Frontier Open Access
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Methodol. Sep 20, 2021; 11(5): 231-242
Published online Sep 20, 2021. doi: 10.5662/wjm.v11.i5.231
Genomics in medicine: A new era in medicine
Vishwanath Pattan, Rahul Kashyap, Vikas Bansal, Narsimha Candula, Thoyaja Koritala, Salim Surani
Vishwanath Pattan, Division of Endocrinology, Wyoming Medical Center, Casper, WY 82601, United States
Rahul Kashyap, Vikas Bansal, Department of Anesthesiology and Peri-operative Medicine, Mayo Clinic, Rochester, MN 55905, United States
Narsimha Candula, Hospital Medicine, University Florida Health, Jacksonville, FL 32209, United States
Thoyaja Koritala, Hospital Medicine, Mayo Clinic Health System, Mankato, MN 56001, United States
Salim Surani, Department of Internal Medicine, Texas A&M University, Corpus Christi, TX 78405, United States
ORCID number: Vishwanath Pattan (0000-0002-7077-8331); Rahul Kashyap (0000-0002-4383-3411); Vikas Bansal (0000-0001-6047-5559); Narsimha Candula (0000-0002-5949-6974); Thoyaja Koritala (0000-0002-1020-9882); Salim Surani (0000-0001-7105-4266).
Author contributions: Pattan V, Kashyap R and Surani S were involved with idea origination, writing and review of manuscript; Bansal V, Candula N and Koritala T were involved in writing and review of literature.
Conflict-of-interest statement: None of the authors have any conflict of interest.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Salim Surani, FACC, FACP, FCCP, MD, Professor, Department of Internal Medicine, Texas A&M University, 701 Ayers Street, Corpus Christi, TX 78405, United States.
Received: January 12, 2021
Peer-review started: January 12, 2021
First decision: June 17, 2021
Revised: June 18, 2021
Accepted: July 19, 2021
Article in press: July 19, 2021
Published online: September 20, 2021


The sequencing of complete human genome revolutionized the genomic medicine. However, the complex interplay of gene-environment-lifestyle and influence of non-coding genomic regions on human health remain largely unexplored. Genomic medicine has great potential for diagnoses or disease prediction, disease prevention and, targeted treatment. However, many of the promising tools of genomic medicine are still in their infancy and their application may be limited because of the limited knowledge we have that precludes its use in many clinical settings. In this review article, we have reviewed the evolution of genomic methodologies/tools, their limitations, and scope, for current and future clinical application.

Key Words: Genomic medicine, Medical genetics, Gene sequencing, DNA sequencing, RNA sequencing, Clustered regularly interspaced short palindromic repeat, Gene based therapy, Genomic tools, Genome editing

Core Tip: The field of Genomics is the future of medicine, as evidenced by the unprecedented research and clinical application which pushed the time boundaries for the coronavirus disease 2019 mRNA vaccines. However the path to unleashing the potential from genomic tools is far from perfect. A thorough research with international collaboration and cooperation is a necessity and the need of the hour.


Understanding the human genome has come a long way since the initial discovery of DNA structure by Watson and Crick in 1953[1]. The genome study and reference used to be a very specialized area, but lately with the advent of the messenger based RNA vaccine have brought the concept of genetics even to the lay public. In the 1970s, the ability to manipulate DNA with recombinant DNA technology increased the horizon. Our understanding of medical genetics began with inheritance patterns of single-gene diseases. The database of Mendelian Inheritance in Man (MIM) was initiated in the early 1960s by McKusick[2]. As of January 5, 2021, 4368 genes were mapped to phenotype-causing mutations[3]. However, only a small portion of diseases have a monogenic cause. The majority of the common diseases are polygenic, and elucidation of their mechanism has remained elusive.

The human genome project, which was completed in 2003, revolutionized the understanding of the human genome and served as a turning point to fast forward the genomic methodologies. However, the clinical application of findings from these genomic studies is still in its infancy. This is largely because we still have not understood or made complete sense of the available information. That is, the sequence data have been difficult to correlate to functional outcomes, making it difficult to understand the genetic basis of diseases and the complex gene-lifestyle-environment influences or their interaction. Moreover, most of the initial focus of the research had been on coding regions of DNA which comprises approximately 2% of the DNA and the knowledge about specific implications of non-coding DNA regions (98% of DNA) are largely unknown[4,5].

Remarkably, the human genome and the closest related species chimpanzees differ in single nucleotide alterations by a mere 1.23% and in deletions, insertions, and copy number variations by 3%[6]. In humans, the genomes of any two individuals are about 99.9% identical. However, a mere 0.1% variation allows for changes in a massive number of nucleotides because the human genome has approximately 30 billion base pairs (3.3 × 109)[7].

In this review, we will discuss the evolution in genomic methodology, limitations, and their scope for current and future clinical application.

DNA sequencing

After the initial DNA sequencing method by Maxam and Gilbert[8] in 1977, the chain-termination DNA sequencing method developed by Sanger et al[9] in 1977 was used for the next few decades. It relied on the template DNA strand and had limited capacity for sequencing gene panels. Subsequently, with commercial production of high throughput technologies or next-generation sequencing (NGS) revolutionized the DNA sequencing by 2007[10]. Also called as massively parallel sequencing, NGS does parallel sequencing of millions of small DNA fragments. Each DNA fragment is fixed at a unique location on the solid support. While the sample of the patient's DNA which serves as a template in NGS is amplified and fragmented, the third-generation sequencing uses single DNA molecules rather than the amplified DNA as a template thus eliminating errors from DNA amplification processes. The NGS can be used for whole-genome sequencing, exome sequencing, or targeted gene panels comprising tens to hundreds of genes.

Single nucleotide polymorphism

Single nucleotide polymorphism (SNP) is the variation in genetic sequence by a single nucleotide. It is the most common type of genetic variation in man[11]. It was detected in the 1980s using restriction enzymes[12]. With application of the microarray technology to SNPs, the scope of SNP in clinical practice has widened, especially in oncology. The first SNP array analysis was done in 1998 and the first application of SNP array analysis in cancer was done in 2000[13]. SNP array analysis is used to determine loss of heterozygosity, allelic imbalance, genomic copy number changes, frequency of homozygous chromosome regions, uniparental disomy, DNA methylation alterations and linkage analysis of DNA polymorphisms in cancer cells[13,14].

DNA amplification

Kary Banks Mullis successfully demonstrated polymerase chain reaction (PCR) in 1983[15]. PCR is a cost-effective method that can amplify a single DNA exponentially[16]. It is a rapid, highly specific, and extremely sensitive method. PCR is being used in SNP genotyping, detection of rare sequences, insertion-deletion variants, and structural variants like copy-number variants.

Linkage and association analysis

Linkage studies have been used for mapping of genes for heritable traits to their chromosomal locations. 1st genetic linkage map was done in 1911 by Sturtevant A[17]. Parametric linkage analysis is used to map the disease-causing gene for monogenic diseases. Here, the logarithm of the odds (LOD) scores and recombination fractions are used to map the gene location. Model-free linkage analysis or non-parametric linkage analysis is used for complex or polygenic diseases, or when the model of inheritance is not known[18]. Linkage analysis of the whole genome can identify large regions of the chromosome with evidence of disease containing the gene[19,20], but this large span of chromosomes can have hundreds of candidate genes.

Linkage studies have been used for mapping Mendelian traits with high penetrance in families and relatives[20]. They are especially useful to identify rare alleles that are present in a small number of families[21], for disease genes with weak effects and polygenic diseases, linkage disequilibrium association mapping has proved to be more useful. In genome-wide association studies (GWAS), genotyping of hundreds or thousands of SNPs is done in cases and control populations and their association with heritability is analyzed. A combination of linkage and association methodologies helps to identify and characterize the wider range of disease-susceptibility variants[22].

Fluorescence in Situ Hybridization (FISH) was developed in 1987. It is a cytogenetic technique which uses fluorescent DNA probes which are designed to label precise chromosomal locations. The advantage of FISH over conventional cytogenetic metaphase karyotype analysis is lack of cell culture requirement. It can rapidly evaluate interphase nuclei in the fresh or paraffin-embedded sample[23]. However, the resolution of this technique is only as good as that of karyotype bands. Cloned DNA FISH probes of about 100 kb, called bacterial artificial chromosomes, are now available. FISH is being utilized more in making clinical diagnosis among Oncology due to its simplicity and reliability to evaluate the key biomarkers in various malignancies.

Comparative genomic hybridization

Comparative genomic hybridization (CGH) was developed in 1992. CGH can detect DNA copy number changes across the entire genome of a patient sample in a single experiment. It compares the hybridization signal intensity of a test sample (for example tumor sample) against a reference sample along the chromosomes[13].


The HapMap project was started in 2002 to develop a haplotype map of the human genome. It can also describe the common patterns of human genetic variation[24]. The 1000 Genomes Project comprised a total of 26 diverse population set in which whole-genome sequencing was performed. It also used deep exome sequencing and dense microarray genotyping to give a comprehensive description of common human genetic variation[25].


It involves modification of the genome at a precise, prespecified locus using programmable nucleases. Examples of some of the programmable nucleases include zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and clustered regularly interspaced short palindromic repeat (CRISPR)-Cas (CRISPR-associated) system. These programmable nucleases are designed to impart site-specific double-strand breaks (dsBs) in chromosomal DNA. The cell is therefore forced to use one of the endogenous DNA repair mechanisms — homologous recombination or homology-directed repair (HDR) and nonhomologous end-joining (NHEJ). This enables targeted genetic modifications during the repair process in the living cells (in vivo) (Table 1)[26]. ZFNs and TALENS recognize the target sequence through protein-DNA interaction. CRISPR-Cas nucleases recognize target sequences through RNA and DNA base pairing[26].

Table 1 Characteristics of commonly used genomic tools.
Tools for genomics
Principle of use
Pros and application
Genome-wide association studies (GWAS)Gene mapping study using DNA microarray to identify the association between SNP and specific risk alleles that are more prevalent in cases than in controls, via linkage disequilibriumHas potential for population-based application. Example — The Severe COVID-19 GWAS Group[34] studied patients with respiratory failure from severe COVID-19 and narrowed down the genetic susceptibility locus to a gene cluster on chromosome locus 3p21.31. They also verified the potential involvement of the ABO blood group systemDoes not establish causality but only an association with SNP; Missing heritability- cannot explain variance in complex traits or genes with a small effect size; Does not account for epigenetic changes and epistasis (gene-gene interaction); GWAS data catalog mostly from individuals of European descent which may limit application in minority population[35]
Expression quantitative trait loci (eQTL) analysisLinks SNPs to changes in gene expression by measuring the expression of many genes simultaneously in microarrays. Helps to narrow down to SNPs more likely to impact the disease conditionProvides better insight into specific causal mechanisms[36]; Liver eQTL — useful in pharmacogenomic studies by analyzing Epistatic eQTL Interactions[37]Limited tissue interrogation will give misleading biological interpretations about the gene mediating the regulatory effect to increase disease risk[38]
Deep sequencing or Next-generation sequencingExome sequencing: 85% of known disease-causing mutations in Mendelian disorders are found in exons. Exome sequencing is a useful tool to find the causal genes for Mendelian disordersReduced cost and limited data to interpret; Linkage study design is unsuitable for extremely rare and sporadic Mendelian disorders for which exome sequencing would be more practical[39]Exome sequencing: It can miss pathogenic variants in a non-coding region. Repetitive regions (e.g., pseudogenes) can confound results in whole-exome sequencing[41]; Potentiate technical biases regarding exon capture limiting its use in detecting copy-number variants as well as in genomic regions where capture is less efficient[42]
Whole-genome sequencing: Can sequence every nucleotide base in the human genome (approximately 3.3 × 109 base pairs)Whole-genome sequencing: Avoids inherent biases of exome captureWhole-genome sequencing: Too much data but little clinical knowledge available to interpret; Higher cost compared to clinical utility
Targeted gene panel: Provides information on prespecified disease-associated genesExamples: Rapid whole-genome sequencing to investigate extensively drug-resistant (XDR) tuberculosis[40]
RNA-seqUses NGS to analyze RNA expression patterns or transcriptome profiling by reverse transcription of RNA sample to complementary DNAs (cDNA) and PCR amplificationCan be used: to analyze RNA expression profile at single cell level or quantify gene expression[43]; to obtain data on novel transcripts and is not limited by availability of reference genome data[44]; to identify alternatively spliced genes; to detect allele-specific gene expression[44]cDNA synthesis and PCR amplification steps can introduce bias and errors[44]
EpigenomicsEpigenomics involves methods used to identify DNA methylation and histone modifications. Sodium bisulfite can identify unmethylated cytosines due to its ability to convert unmethylated cytosines to uracil. However the methylated cytosine is resistant to this conversion. Methylation-dependent restriction enzymes are used for DNA methylation analysis[45]. Chromatin immunoprecipitation (ChIP) is used for the investigation of histone modificationsChIP allows precise mapping of the DNA-protein interaction in living cells. Cross-linked protein-DNA complex can be treated with exonucleases to remove cross-linked DNA sequences that are not avidly bound to protein of interest. This is called ChIP-Exo. This allows mapping of in vivo protein occupancy at single nucleotide-level resolution[47]Needs design of antibodies specific to DNA-bound protein of interest which could be modified histone or transcription factors
Immunoprecipitation techniques: ChIP on Chip; ChIP-Seq. Chromatin is isolated from the sample and the DNA involved in DNA protein cross-linked complex is isolated using antibodies specific to the DNA-bound protein. The isolated DNA is amplified using PCR and analyzed using gel electrophoresis imaging, microarray hybridization (ChIP-chip), or direct sequencing with NGS (ChIP-Seq)[46]
TranscriptomicsNorthern blot: RNA molecules separated by gel electrophoresis by size and subsequently hybridized with labeled complementary ssDNA and detected using chemic luminescence or autoradiographyNorthern blot can both quantify the amount of RNA and also determine the size of mRNA transcript. Can detect transcript variant of genes[49]Northern blot-need radioactive probes and has lower sensitivity
Ribonuclease (RNase) protection assay: Differs from northern blot by use of antisense RNA probes called riboprobesRNase protection assay: It can simultaneously detect and quantify multiple mRNA targets in a single RNA sample .It has high sensitivityRNase protection assay: Does not provide information on transcript size[52]
Real-time RT-PCR: cDNA are synthesized by reverse transcription from the sample RNA identified. The resulting cDNA is amplified by using fluorescently labeled oligonucleotide primers. Fluorescence intensity is monitored and correlated with several PCR cyclesReal-time RT-PCR: Allows quantitative genotyping, detection of SNPs and allelic variants or genetic variations even when mutation is found in very small fraction of cells in the sample. Has become clinical standard for diagnoses in Infectious diseases and it’s role is evolving rapidly in cancer diagnostics[50]Real-time RT-PCR: The process is complex and any errors in choice of reagents, primers or probes will affect accuracy. There could be risk for errors during data analysis and reporting. The process is expensive[53]
In situ hybridization: Tissue specimen is fixed to preserve morphology and then treated with proteases. A labeled probe is hybridized to the sample and detected using chemiluminescence or autoradiography[48]In situ hybridization: Very useful in diagnostic application when there is limited tissue sample (in embryos and biopsy specimen). Several specific hybridizations can be done on the same sample. Tissue samples can be freeze for future use[48]In situ hybridization: Low diagnostic yield when the sample has low DNA and RNA copies[48]
Spotted DNA arrays: Measures relative expression levels between 2 samples. cDNA probes amplified by PCR are spotted on a glass slide and then mRNAs are isolated from the samples. The mRNA from each sample is labeled with different fluorescent dyes. The samples are mixed, co-hybridized with cDNA probes on glass slides to measure relative gene expressionSpotted DNA arrays: The major application of DNA array is measurement of gene expression levels[51]Spotted DNA arrays: DNA array can only detect known sequences, that were used to construct the array. It only gives relative estimate of gene expression and not reliable for absolute quantification. When the genome has multiple related sequences then design of array that distinguishes these sequences is challenging. Difficult to reproduce the array[51]

In the year 2013, Cong et al[27] and Mali et al[28] showed successful genome editing in mammalian cells using the CRISPR system. In the last 5 years, we have seen a leap in the research interest (both animal and human) in CRISPR genomic editing.

While genome editing holds promise to correct the defective genome in vivo, therapies can also be designed to alter the gene expression without altering the genomic code. For example, anti-sense oligonucleotide can be used to alter the splice points of pre-mRNA to correct for a defective gene or suppress its expression. Examples of drugs which use splice modulation and approved by Food and Drug Administration (FDA) are Eteplirsen (exon skipping, approved for Duchenne muscular dystrophy) and nusinersen (exon inclusion, approved for spinal muscular atrophy)[29].

Table 1 summarizes the commonly used genomic tools, their working principle, advantages/applications and limitations (see Table 1). Table 2 summarizes the major genome/gene editing tools their working principle, advantages/applications and limitations. Table 3 summarizes gene-based therapies that are either FDA approved therapies or investigational therapies showing promise.

Table 2 Characteristics of genome-editing technologies using programmable nucleases.
Gene editing
Principle of use
Advantages or application
CRISPR-Cas9 guided gene editing: (1)NHEJ; and (2)HDRCas9 enzyme (an endonuclease) cleaves ds- DNA at a specific site as determined by the specific sequence of the guide RNA. Genome editing is done when the cell tries to repair the dsB (either via NHEJ or HDR)Has the potential to edit genes in almost any cell type in vivo; Has potential in every field, notably infections[54], genetic disease[55], cancer[56] etc.; CRISPR-Cas9 can also be used for large scale loss-of-function gene screen: Catalytically inactive Cas9 (dCas9) can be directed by guide RNA, bind to specific genes to reversibly suppress or activate gene transcription (by fusion of transcription activators or suppressors with dCas9)[57]; Epigenetic modulators (e.g., DNA methylase) can also be fused with dCas9 to achieve controlled epigenetic modulations. Cas-9 NHEJ is simpler and efficient; Cas-9 HDR is more precise but lower efficiency than NHEJ. The mutant version of the Cas9 called Cas9 nickase can be used to minimize the risk of off-targetsThe off-target activity of RNA-guided endonuclease-induced mutations[58]. Off-target mutations with a frequency below 0.5% cannot be detected by current off-target detection techniques[59]
Augmented CRISPR-Cas12a systemCas12a cuts target ds- DNA. However, unlike Cas9, Cas12a subsequently becomes activated and causes indiscriminate cleavage of ssDNA causing collateral damage. SARS-CoV-2 RNA DETECTR Assay: samples from upper airway swabs are processed using simultaneous reverse transcription and isothermal amplification with loop-mediated amplification (RT-LAMP). Subsequently the Cas12 enzyme is addedCRISPR-Cas12a system can be used to create new drug or cell delivery systems and bio-sensing (e.g., to detect methicillin-resistant Staphylococcus aureus, Ebola virus[60]. Emergency Use Authorization (EUA) Only for qualitative detection of nucleic acid from the SARS-CoV-2 in upper respiratory specimens[61,62]Limited research data and application. The technology is still in its infancy
CRISPR-Cas 13CRISPR-Cas 13 system can be used via SHERLOCK technique for ultra-sensitive detection of RNA or DNA from the clinical samplesSherlockTM CRISPR SARS-CoV-2 kit: Emergency Use Authorization (EUA) qualitative for detection of nucleic acid fromSARS-CoV-2 in upper respiratory specimens[63,64]
Prime editorsIt uses a catalytically impaired Cas9 which is fused to an engineered reverse transcriptase and prime editing guide RNA. The guide RNA specifies the target site and encodes the desired sequencePrime editing is associated with fewer off-target edits when compared with conventional CRISPR-Cas system[65]. Anzalone et al[66] applied prime editing in human cells to correct the primary genetic causes of sickle cell disease and Tay-Sachs disease. It does not require double-strand breaks or donor DNA templatesResearch literature on application of prime editing is limited. Unlike conventional CRISPR-Cas system prime editing may not be able to provide large DNA insertions or deletions[65]
Zinc finger nucleasesZinc finger nuclease (dimer of zinc finger hybrid bound to restriction endonuclease) is a programmable nuclease that cleaves specific sites in DNA. They recognize the target sequence through protein-DNA interactionPotential for plant genome editing for crop improvement[67]Necessity to engineer novel proteins for each target site: Expensive; Difficult to reproduce
TALENSTAL proteins have TAL effector DNA-binding domain fused to a DNA cleavage domain. TALENs create dsBs that require repair by NHEJ or HDRThe DNA-binding specificity of TALEs is easier to engineer than zinc-fingerProteins[68]Necessity to engineer novel proteins for each target site. TALENs are large and pose packaging challenge in viral delivery systems[69]
Table 3 Gene based therapies: List of Food and Drug Administration approved therapies and investigational therapies showing promise.
Therapy or drug
Mechanism of action
Approval status
Janssen COVID-19 vaccinePrevention of 2019 coronavirus disease (COVID-19) for individuals 18 yr of age and olderRecombinant, humanadenovirus type 26 vector which expresses the SARS-CoV-2 “S” antigen after entering human cells thus eliciting immune response against COVID-19Emergency use authorization (EUA) on February 27, 2021[70]. Pause placed on vaccine use on April 13, 2021[71]. FDA lifted vaccination pause on April 23, 2021[72]
Pfizer-BioNTech COVID-19 Vaccine[73-75]Prevention of COVID-19 for individuals 16 yr of age and oldermodRNA forumated in lipid particles when delivered to host cells express SARS-CoV-2 “S” antigen, thus eliciting immune response against COVID-19EUA on December 11, 2020
Moderna COVID-19 vaccine[76-78]Prevention of COVID-19 for individuals 18 yr of age and oldermodRNA forumated in lipid particles when delivered to host cells express SARS-CoV-2 “S” antigen, thus eliciting immune response against COVID-19EUA on December 18, 2020
Lumasiran[79]Primary hyperoxaluria type 1HAO1-directed small interfering ribonucleic acidApproved in Nov 2020
Viltolarsen[80]Duchenne muscular dystrophyAntisense oligonucleotide directed to exon 53 skippingApproved in August 2020
Brexucabtagene autoleucel[81]Relapsed/refractory mantle cell lymphomaGenetically modified autologous CD19 T cells directed against CD19 expressing cancer cellsApproved in July 2020
Golodirsen[82]Duchenne muscular dystrophyAntisense oligonucleotide directedApproved in December 2019
Givosiran[83]Acute hepatic porphyriaDouble-stranded small interfering RNA that degrades the ALAS1 mRNA in hepatocytes via RNA interferenceApproved in November 2019
Onasemnogene abeparvovec-xioi[84]Spinal muscular atrophy (SMA)AAV9-based gene therapy which encodes the human SMN proteinApproved in May 2019
Inotersen[85]Polyneuropathy of hereditary transthyretin-mediated amyloidosisTransthyretin-directed antisense oligonucleotideApproved in October 2018
Axicabtagene ciloleucel[86]Relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapyGenetically modified autologous CD19 T cells directed against CD19 expressing cancer cellsApproved in October 2017
Tisagenlecleucel[87]Refractory or relapsed B-cell precursor acute lymphoblastic leukemia (ALL)Genetically modified autologous CD19 T cells directed against CD19 expressing cancer cellsApproved in August 2017
Nusinersen[88]SMASurvival motor neuron-2 (SMN2)-directed antisense oligonucleotideApproved in December 2016
Eteplirsen[89]Duchenne muscular dystrophyAntisense oligonucleotid that binds to exon 51 of dystrophin pre-mRNAApproved in September 2016
Talimogene laherparepvec[90]Genetically modified herpes simplex virus, type 1 used as oncolytic viral therapyThey utilized the local treatment of unresectable cutaneous, subcutaneous, and nodal lesions in patients with melanoma who had the recurrence after the initial surgeryApproved in October 2015
Giroctocogene fitelparvovec[91]Moderately severe to severe hemophilia AFactor VIII gene delivery using recombinant adeno-associated viruses as vectorsInvestigational in phase 3 trial
Inclisiran[92]Heterozygous and possibly homozygous familial hypercholesterolemiaSmall-interfering ribonucleic acid which decreases hepatic production of PCSK9Investigational phase 3 trial
Volanesorsen[93]Familial chylomicronemia syndromeAntisense oligonucleotide that targets the messenger RNA for apo-CIIIConditional approval by European Medicines Agency’s (EMA) but not by FDA
CRISPR-Cas9 gene editing[94]Sickle cell disease and β-thalassemiaCRISPR-Cas9based allele editing of the BCL11A erythroid-specific enhancer in autologous CD34+ cellsInvestigational- FDA Fast Track Designation for CTX001 in sickle cell disease

The newer genomic technology and tools have broadened the scope and pushed the time limits for development of new diagnostic kits, preventive strategies like vaccines, therapeutic strategies like gene modulation and gene therapy. A lot is yet to be studied in terms of the complex interaction of gene-environment-lifestyle-disease. Knowing the impact of genomics on disease pathophysiology and response to medications[30]. expands the scope of research and clinical application. While genome editing holds promise to correct the defective genome in vivo, therapies can also be designed to alter the gene expression without altering the genomic code (example exon skipping, or inclusion discussed above).

The newer genomic editing tools have showed great potential and promise but they need to be studied extensively before clinical application. Also, uniform international ethical guidelines and guiding principles need to be established so that these genomic technologies are not misused.

It is very important to include diverse populations and to represent minority population in the genomic studies, so that results could be generalized and more accurate diagnostic, predictive and therapeutic tools can be developed.

Genomics in medicine is indeed a new era in medicine. Even the control of coronavirus disease 2019 pandemic[31] has just begun at the time of writing of this article with gene based therapies eliciting immune response against severe acute respiratory syndrome coronavirus 2 spike proteins. A unified international collaboration[32,33] is needed to continue expanding gene therapy use in opening new frontiers for fight against novel infections and disease.


Genomic medicine holds great promise for providing insight into disease pathophysiology, provide better diagnostic or disease predictive tools, preventive therapies and finally for targeted treatment of diseases. Although some of the newer tools (like CRISPR system) have great potential, more research is needed before these tools can be unleashed to clinical use. Hence there is great need for studies to unravel the mystery of complex interaction of both coding and noncoding genomic regions with environment and lifestyle influences on disease occurrence and management.


Manuscript source: Invited manuscript

Specialty type: Medical laboratory technology

Country/Territory of origin: United States

Peer-review report’s scientific quality classification

Grade A (Excellent): 0

Grade B (Very good): 0

Grade C (Good): C

Grade D (Fair): 0

Grade E (Poor): 0

P-Reviewer: Taheri S S-Editor: Gao CC L-Editor: A P-Editor: Guo X

1.  Watson JD, Crick FH. The structure of DNA. Cold Spring Harb Symp Quant Biol. 1953;18:123-131.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 563]  [Cited by in F6Publishing: 53]  [Article Influence: 8.3]  [Reference Citation Analysis (0)]
2.  McKusick VA. Mendelian Inheritance in Man and its online version, OMIM. Am J Hum Genet. 2007;80:588-604.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 468]  [Cited by in F6Publishing: 148]  [Article Influence: 33.4]  [Reference Citation Analysis (0)]
3.  Johns Hopkins University  OMIM Gene Map Statistics. [cited 20 December 2020]. In: Johns Hopkins University [Internet]. Available from:  [PubMed]  [DOI]  [Cited in This Article: ]
4.  Ling H, Vincent K, Pichler M, Fodde R, Berindan-Neagoe I, Slack FJ, Calin GA. Junk DNA and the long non-coding RNA twist in cancer genetics. Oncogene. 2015;34:5003-5011.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 199]  [Cited by in F6Publishing: 119]  [Article Influence: 33.2]  [Reference Citation Analysis (0)]
5.  Gloss BS, Dinger ME. Realizing the significance of noncoding functionality in clinical genomics. Exp Mol Med. 2018;50:1-8.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 42]  [Cited by in F6Publishing: 17]  [Article Influence: 14.0]  [Reference Citation Analysis (0)]
6.  Suntsova MV, Buzdin AA. Differences between human and chimpanzee genomes and their implications in gene expression, protein functions and biochemical properties of the two species. BMC Genomics. 2020;21:535.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 2]  [Cited by in F6Publishing: 2]  [Article Influence: 2.0]  [Reference Citation Analysis (0)]
7.  Gyles C. The DNA revolution. Can Vet J. 2008;49:745-746.  [PubMed]  [DOI]  [Cited in This Article: ]
8.  Maxam AM, Gilbert W. A new method for sequencing DNA. Proc Natl Acad Sci U S A. 1977;74:560-564.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 4025]  [Cited by in F6Publishing: 1893]  [Article Influence: 91.5]  [Reference Citation Analysis (0)]
9.  Sanger F, Nicklen S, Coulson AR. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977;74:5463-5467.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 38765]  [Cited by in F6Publishing: 11272]  [Article Influence: 901.5]  [Reference Citation Analysis (0)]
10.  Reuter JA, Spacek DV, Snyder MP. High-throughput sequencing technologies. Mol Cell. 2015;58:586-597.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 526]  [Cited by in F6Publishing: 130]  [Article Influence: 87.7]  [Reference Citation Analysis (0)]
11.  Shen LX, Basilion JP, Stanton VP Jr. Single-nucleotide polymorphisms can cause different structural folds of mRNA. Proc Natl Acad Sci U S A. 1999;96:7871-7876.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 193]  [Cited by in F6Publishing: 76]  [Article Influence: 8.8]  [Reference Citation Analysis (0)]
12.  Gray IC, Campbell DA, Spurr NK. Single nucleotide polymorphisms as tools in human genetics. Hum Mol Genet. 2000;9:2403-2408.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 146]  [Cited by in F6Publishing: 37]  [Article Influence: 7.0]  [Reference Citation Analysis (0)]
13.  Mao X, Young BD, Lu YJ. The application of single nucleotide polymorphism microarrays in cancer research. Curr Genomics. 2007;8:219-228.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 41]  [Cited by in F6Publishing: 12]  [Article Influence: 4.1]  [Reference Citation Analysis (0)]
14.  Sato-Otsubo A, Sanada M, Ogawa S. Single-nucleotide polymorphism array karyotyping in clinical practice: where, when, and how? Semin Oncol. 2012;39:13-25.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 27]  [Cited by in F6Publishing: 6]  [Article Influence: 3.0]  [Reference Citation Analysis (0)]
15.  Fairfax MR, Salimnia H. Diagnostic molecular microbiology: a 2013 snapshot. Clin Lab Med. 2013;33:787-803.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 7]  [Cited by in F6Publishing: 2]  [Article Influence: 1.0]  [Reference Citation Analysis (0)]
16.  Wages JM  Polymerase Chain Reaction. In: Worsfold P, Townshend A, Poole C. Encyclopedia of Analytical Science. Oxford: Elsevier, 2005: 243-250.  [PubMed]  [DOI]  [Cited in This Article: ]
17.  Griffiths AJ, Miller JH, Suzuki DT, Lewontin RC, Gelbart WM.   An Introduction to Genetic Analysis - NCBI Bookshelf. 7th ed. New York: W. H. Freeman, 2000.  [PubMed]  [DOI]  [Cited in This Article: ]
18.  Dawn Teare M, Barrett JH. Genetic linkage studies. Lancet. 2005;366:1036-1044.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 120]  [Cited by in F6Publishing: 21]  [Article Influence: 7.5]  [Reference Citation Analysis (0)]
19.  Ott J, Wang J, Leal SM. Genetic linkage analysis in the age of whole-genome sequencing. Nat Rev Genet. 2015;16:275-284.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 157]  [Cited by in F6Publishing: 33]  [Article Influence: 26.2]  [Reference Citation Analysis (0)]
20.  Pulst SM. Genetic linkage analysis. Arch Neurol. 1999;56:667-672.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 36]  [Cited by in F6Publishing: 8]  [Article Influence: 1.6]  [Reference Citation Analysis (0)]
21.  Hinrichs AL, Suarez BK. Incorporating linkage information into a common disease/rare variant framework. Genet Epidemiol. 2011;35 Suppl 1:S74-S79.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 10]  [Cited by in F6Publishing: 4]  [Article Influence: 1.1]  [Reference Citation Analysis (0)]
22.  Ott J, Kamatani Y, Lathrop M. Family-based designs for genome-wide association studies. Nat Rev Genet. 2011;12:465-474.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 194]  [Cited by in F6Publishing: 48]  [Article Influence: 19.4]  [Reference Citation Analysis (0)]
23.  Hu L, Ru K, Zhang L, Huang Y, Zhu X, Liu H, Zetterberg A, Cheng T, Miao W. Fluorescence in situ hybridization (FISH): an increasingly demanded tool for biomarker research and personalized medicine. Biomark Res. 2014;2:3.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 43]  [Cited by in F6Publishing: 9]  [Article Influence: 6.1]  [Reference Citation Analysis (0)]
24.  National Human Genome Research Institute  The International HapMap Project. Updated 06/04/2012. [cited 10 December 2020]. In: National Human Genome Research Institute [Internet]. Available from:  [PubMed]  [DOI]  [Cited in This Article: ]
25.  1000 Genomes Project Consortium; Auton A, Brooks LD, Durbin RM, Garrison EP, Kang HM, Korbel JO, Marchini JL, McCarthy S, McVean GA, Abecasis GR. A global reference for human genetic variation. Nature. 2015;526:68-74.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 8153]  [Cited by in F6Publishing: 2346]  [Article Influence: 1358.8]  [Reference Citation Analysis (0)]
26.  Kim H, Kim JS. A guide to genome engineering with programmable nucleases. Nat Rev Genet. 2014;15:321-334.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 759]  [Cited by in F6Publishing: 260]  [Article Influence: 108.4]  [Reference Citation Analysis (0)]
27.  Cong L, Ran FA, Cox D, Lin S, Barretto R, Habib N, Hsu PD, Wu X, Jiang W, Marraffini LA, Zhang F. Multiplex genome engineering using CRISPR/Cas systems. Science. 2013;339:819-823.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 8822]  [Cited by in F6Publishing: 3160]  [Article Influence: 1102.8]  [Reference Citation Analysis (0)]
28.  Mali P, Yang L, Esvelt KM, Aach J, Guell M, DiCarlo JE, Norville JE, Church GM. RNA-guided human genome engineering via Cas9. Science. 2013;339:823-826.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 5766]  [Cited by in F6Publishing: 2250]  [Article Influence: 720.8]  [Reference Citation Analysis (0)]
29.  Lim KRQ, Yokota T. Invention and Early History of Exon Skipping and Splice Modulation. Methods Mol Biol. 2018;1828:3-30.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 11]  [Cited by in F6Publishing: 8]  [Article Influence: 5.5]  [Reference Citation Analysis (0)]
30.  Pattan V, Seth S, Jehangir W, Bhargava B, Maulik SK. Effect of Atorvastatin and Pioglitazone on Plasma Levels of Adhesion Molecules in Non-Diabetic Patients With Hypertension or Stable Angina or Both. J Clin Med Res. 2015;7:613-619.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in F6Publishing: 1]  [Reference Citation Analysis (0)]
31.  Shah A, Kashyap R, Tosh P, Sampathkumar P, O'Horo JC. Guide to Understanding the 2019 Novel Coronavirus. Mayo Clin Proc. 2020;95:646-652.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 39]  [Cited by in F6Publishing: 26]  [Article Influence: 39.0]  [Reference Citation Analysis (0)]
32.  Walkey AJ, Kumar VK, Harhay MO, Bolesta S, Bansal V, Gajic O, Kashyap R. The Viral Infection and Respiratory Illness Universal Study (VIRUS): An International Registry of Coronavirus 2019-Related Critical Illness. Crit Care Explor. 2020;2:e0113.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 16]  [Cited by in F6Publishing: 7]  [Article Influence: 16.0]  [Reference Citation Analysis (0)]
33.  Walkey AJ, Sheldrick RC, Kashyap R, Kumar VK, Boman K, Bolesta S, Zampieri FG, Bansal V, Harhay MO, Gajic O. Guiding Principles for the Conduct of Observational Critical Care Research for Coronavirus Disease 2019 Pandemics and Beyond: The Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study Registry. Crit Care Med. 2020;48:e1038-e1044.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 7]  [Cited by in F6Publishing: 2]  [Article Influence: 7.0]  [Reference Citation Analysis (0)]
34.  Severe Covid-19 GWAS Group; Ellinghaus D, Degenhardt F, Bujanda L, Buti M, Albillos A, Invernizzi P, Fernández J, Prati D, Baselli G, Asselta R, Grimsrud MM, Milani C, Aziz F, Kässens J, May S, Wendorff M, Wienbrandt L, Uellendahl-Werth F, Zheng T, Yi X, de Pablo R, Chercoles AG, Palom A, Garcia-Fernandez AE, Rodriguez-Frias F, Zanella A, Bandera A, Protti A, Aghemo A, Lleo A, Biondi A, Caballero-Garralda A, Gori A, Tanck A, Carreras Nolla A, Latiano A, Fracanzani AL, Peschuck A, Julià A, Pesenti A, Voza A, Jiménez D, Mateos B, Nafria Jimenez B, Quereda C, Paccapelo C, Gassner C, Angelini C, Cea C, Solier A, Pestaña D, Muñiz-Diaz E, Sandoval E, Paraboschi EM, Navas E, García Sánchez F, Ceriotti F, Martinelli-Boneschi F, Peyvandi F, Blasi F, Téllez L, Blanco-Grau A, Hemmrich-Stanisak G, Grasselli G, Costantino G, Cardamone G, Foti G, Aneli S, Kurihara H, ElAbd H, My I, Galván-Femenia I, Martín J, Erdmann J, Ferrusquía-Acosta J, Garcia-Etxebarria K, Izquierdo-Sanchez L, Bettini LR, Sumoy L, Terranova L, Moreira L, Santoro L, Scudeller L, Mesonero F, Roade L, Rühlemann MC, Schaefer M, Carrabba M, Riveiro-Barciela M, Figuera Basso ME, Valsecchi MG, Hernandez-Tejero M, Acosta-Herrera M, D'Angiò M, Baldini M, Cazzaniga M, Schulzky M, Cecconi M, Wittig M, Ciccarelli M, Rodríguez-Gandía M, Bocciolone M, Miozzo M, Montano N, Braun N, Sacchi N, Martínez N, Özer O, Palmieri O, Faverio P, Preatoni P, Bonfanti P, Omodei P, Tentorio P, Castro P, Rodrigues PM, Blandino Ortiz A, de Cid R, Ferrer R, Gualtierotti R, Nieto R, Goerg S, Badalamenti S, Marsal S, Matullo G, Pelusi S, Juzenas S, Aliberti S, Monzani V, Moreno V, Wesse T, Lenz TL, Pumarola T, Rimoldi V, Bosari S, Albrecht W, Peter W, Romero-Gómez M, D'Amato M, Duga S, Banales JM, Hov JR, Folseraas T, Valenti L, Franke A, Karlsen TH. Genomewide Association Study of Severe Covid-19 with Respiratory Failure. N Engl J Med. 2020;383:1522-1534.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 597]  [Cited by in F6Publishing: 266]  [Article Influence: 597.0]  [Reference Citation Analysis (0)]
35.  Mills MC, Rahal C. A scientometric review of genome-wide association studies. Commun Biol. 2019;2:9.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 123]  [Cited by in F6Publishing: 48]  [Article Influence: 61.5]  [Reference Citation Analysis (0)]
36.  Battle A, Montgomery SB. Determining causality and consequence of expression quantitative trait loci. Hum Genet. 2014;133:727-735.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 37]  [Cited by in F6Publishing: 14]  [Article Influence: 5.3]  [Reference Citation Analysis (0)]
37.  Glubb DM, Dholakia N, Innocenti F. Liver expression quantitative trait loci: a foundation for pharmacogenomic research. Front Genet. 2012;3:153.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 11]  [Cited by in F6Publishing: 3]  [Article Influence: 1.2]  [Reference Citation Analysis (0)]
38.  Nica AC, Dermitzakis ET. Expression quantitative trait loci: present and future. Philos Trans R Soc Lond B Biol Sci. 2013;368:20120362.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 204]  [Cited by in F6Publishing: 55]  [Article Influence: 25.5]  [Reference Citation Analysis (0)]
39.  Ku CS, Naidoo N, Pawitan Y. Revisiting Mendelian disorders through exome sequencing. Hum Genet. 2011;129:351-370.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 163]  [Cited by in F6Publishing: 51]  [Article Influence: 16.3]  [Reference Citation Analysis (0)]
40.  Köser CU, Bryant JM, Becq J, Török ME, Ellington MJ, Marti-Renom MA, Carmichael AJ, Parkhill J, Smith GP, Peacock SJ. Whole-genome sequencing for rapid susceptibility testing of M. tuberculosis. N Engl J Med. 2013;369:290-292.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 168]  [Cited by in F6Publishing: 49]  [Article Influence: 21.0]  [Reference Citation Analysis (0)]
41.  Zhang Y, Li S, Abyzov A, Gerstein MB. Landscape and variation of novel retroduplications in 26 human populations. PLoS Comput Biol. 2017;13:e1005567.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 17]  [Cited by in F6Publishing: 6]  [Article Influence: 4.3]  [Reference Citation Analysis (0)]
42.  Rabbani B, Tekin M, Mahdieh N. The promise of whole-exome sequencing in medical genetics. J Hum Genet. 2014;59:5-15.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 266]  [Cited by in F6Publishing: 80]  [Article Influence: 33.3]  [Reference Citation Analysis (0)]
43.  Tang F, Barbacioru C, Wang Y, Nordman E, Lee C, Xu N, Wang X, Bodeau J, Tuch BB, Siddiqui A, Lao K, Surani MA. mRNA-Seq whole-transcriptome analysis of a single cell. Nat Methods. 2009;6:377-382.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 1532]  [Cited by in F6Publishing: 628]  [Article Influence: 127.7]  [Reference Citation Analysis (0)]
44.  Kukurba KR, Montgomery SB. RNA Sequencing and Analysis. Cold Spring Harb Protoc. 2015;2015:951-969.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 208]  [Cited by in F6Publishing: 55]  [Article Influence: 34.7]  [Reference Citation Analysis (0)]
45.  Gasperskaja E, Kučinskas V. The most common technologies and tools for functional genome analysis. Acta Med Litu. 2017;24:1-11.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 20]  [Cited by in F6Publishing: 6]  [Article Influence: 5.0]  [Reference Citation Analysis (0)]
46.  Pillai S, Chellappan SP. ChIP on chip and ChIP-Seq assays: genome-wide analysis of transcription factor binding and histone modifications. Methods Mol Biol. 2015;1288:447-472.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 5]  [Cited by in F6Publishing: 4]  [Article Influence: 0.8]  [Reference Citation Analysis (0)]
47.  Rhee HS, Pugh BF. ChIP-exo method for identifying genomic location of DNA-binding proteins with near-single-nucleotide accuracy. Curr Protoc Mol Biol. 2012;Chapter 21:Unit 21.24.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 83]  [Cited by in F6Publishing: 24]  [Article Influence: 10.4]  [Reference Citation Analysis (0)]
48.  Jensen E. Technical review: In situ hybridization. Anat Rec (Hoboken). 2014;297:1349-1353.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 41]  [Cited by in F6Publishing: 14]  [Article Influence: 5.9]  [Reference Citation Analysis (0)]
49.  He SL, Green R. Northern blotting. Methods Enzymol. 2013;530:75-87.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 7]  [Cited by in F6Publishing: 1]  [Article Influence: 1.0]  [Reference Citation Analysis (0)]
50.  Deepak S, Kottapalli K, Rakwal R, Oros G, Rangappa K, Iwahashi H, Masuo Y, Agrawal G. Real-Time PCR: Revolutionizing Detection and Expression Analysis of Genes. Curr Genomics. 2007;8:234-251.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 94]  [Cited by in F6Publishing: 24]  [Article Influence: 9.4]  [Reference Citation Analysis (0)]
51.  Bumgarner R. Overview of DNA microarrays: types, applications, and their future. Curr Protoc Mol Biol. 2013;Chapter 22:Unit 22.1..  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 132]  [Cited by in F6Publishing: 36]  [Article Influence: 16.5]  [Reference Citation Analysis (0)]
52.  Qu Y, Boutjdir M. RNase protection assay for quantifying gene expression levels. Methods Mol Biol. 2007;366:145-158.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 10]  [Cited by in F6Publishing: 4]  [Article Influence: 0.7]  [Reference Citation Analysis (0)]
53.  Bustin SA, Nolan T. Pitfalls of quantitative real-time reverse-transcription polymerase chain reaction. J Biomol Tech. 2004;15:155-166.  [PubMed]  [DOI]  [Cited in This Article: ]
54.  Xu L, Wang J, Liu Y, Xie L, Su B, Mou D, Wang L, Liu T, Wang X, Zhang B, Zhao L, Hu L, Ning H, Zhang Y, Deng K, Liu L, Lu X, Zhang T, Xu J, Li C, Wu H, Deng H, Chen H. CRISPR-Edited Stem Cells in a Patient with HIV and Acute Lymphocytic Leukemia. N Engl J Med. 2019;381:1240-1247.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 146]  [Cited by in F6Publishing: 46]  [Article Influence: 73.0]  [Reference Citation Analysis (0)]
55.  Wu SS, Li QC, Yin CQ, Xue W, Song CQ. Advances in CRISPR/Cas-based Gene Therapy in Human Genetic Diseases. Theranostics. 2020;10:4374-4382.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 18]  [Cited by in F6Publishing: 9]  [Article Influence: 18.0]  [Reference Citation Analysis (0)]
56.  Tian X, Gu T, Patel S, Bode AM, Lee MH, Dong Z. CRISPR/Cas9 - An evolving biological tool kit for cancer biology and oncology. NPJ Precis Oncol. 2019;3:8.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 25]  [Cited by in F6Publishing: 20]  [Article Influence: 12.5]  [Reference Citation Analysis (0)]
57.  Lu XJ, Xue HY, Ke ZP, Chen JL, Ji LJ. CRISPR-Cas9: a new and promising player in gene therapy. J Med Genet. 2015;52:289-296.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 94]  [Cited by in F6Publishing: 34]  [Article Influence: 15.7]  [Reference Citation Analysis (0)]
58.  Cho GY, Schaefer KA, Bassuk AG, Tsang SH, Mahajan VB. CRISPR GENOME SURGERY IN THE RETINA IN LIGHT OF OFF-TARGETING. Retina. 2018;38:1443-1455.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 7]  [Cited by in F6Publishing: 2]  [Article Influence: 2.3]  [Reference Citation Analysis (0)]
59.  Kang SH, Lee WJ, An JH, Lee JH, Kim YH, Kim H, Oh Y, Park YH, Jin YB, Jun BH, Hur JK, Kim SU, Lee SH. Prediction-based highly sensitive CRISPR off-target validation using target-specific DNA enrichment. Nat Commun. 2020;11:3596.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 7]  [Cited by in F6Publishing: 4]  [Article Influence: 7.0]  [Reference Citation Analysis (0)]
60.  English MA, Soenksen LR, Gayet RV, de Puig H, Angenent-Mari NM, Mao AS, Nguyen PQ, Collins JJ. Programmable CRISPR-responsive smart materials. Science. 2019;365:780-785.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 105]  [Cited by in F6Publishing: 31]  [Article Influence: 105.0]  [Reference Citation Analysis (0)]
61.  Broughton JP, Deng X, Yu G, Fasching CL, Servellita V, Singh J, Miao X, Streithorst JA, Granados A, Sotomayor-Gonzalez A, Zorn K, Gopez A, Hsu E, Gu W, Miller S, Pan CY, Guevara H, Wadford DA, Chen JS, Chiu CY. CRISPR-Cas12-based detection of SARS-CoV-2. Nat Biotechnol. 2020;38:870-874.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 667]  [Cited by in F6Publishing: 315]  [Article Influence: 667.0]  [Reference Citation Analysis (0)]
62.  U. S. Food and Drug Administration. SARS-CoV-2 RNA DETECTR Assay Accelerated Emergency Use Authorization (EUA) Summary SARS-COV-2 RNA Detectr Assay (UCSF Health Clinical Laboratories, UCSF Clinical Labs at China Basin). [cited 10 December 2020].  In: U.S. Food and Drug Administration [Internet]. Available from:  [PubMed]  [DOI]  [Cited in This Article: ]
63.  Joung J, Ladha A, Saito M, Segel M, Bruneau R, Huang MW, Kim NG, Yu X, Li J, Walker BD, Greninger AL, Jerome KR, Gootenberg JS, Abudayyeh OO, Zhang F. Point-of-care testing for COVID-19 using SHERLOCK diagnostics. medRxiv. 2020;.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 94]  [Cited by in F6Publishing: 12]  [Article Influence: 94.0]  [Reference Citation Analysis (0)]
64.  U. S. Food and Drug Administration. Instructions For Use Sherlock Tm Crispr SARS-CoV-2 kit.[cited 10 December 2020].  In: U.S. Food and Drug Administration [Internet]. Available from:  [PubMed]  [DOI]  [Cited in This Article: ]
65.  Matsoukas IG. Prime Editing: Genome Editing for Rare Genetic Diseases Without Double-Strand Breaks or Donor DNA. Front Genet. 2020;11:528.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 8]  [Cited by in F6Publishing: 6]  [Article Influence: 8.0]  [Reference Citation Analysis (0)]
66.  Anzalone AV, Randolph PB, Davis JR, Sousa AA, Koblan LW, Levy JM, Chen PJ, Wilson C, Newby GA, Raguram A, Liu DR. Search-and-replace genome editing without double-strand breaks or donor DNA. Nature. 2019;576:149-157.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 895]  [Cited by in F6Publishing: 354]  [Article Influence: 447.5]  [Reference Citation Analysis (0)]
67.  Davies JP, Kumar S, Sastry-Dent L. Use of Zinc-Finger Nucleases for Crop Improvement. Prog Mol Biol Transl Sci. 2017;149:47-63.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 10]  [Cited by in F6Publishing: 2]  [Article Influence: 2.5]  [Reference Citation Analysis (0)]
68.  Kim MS, Kini AG. Engineering and Application of Zinc Finger Proteins and TALEs for Biomedical Research. Mol Cells. 2017;40:533-541.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 11]  [Cited by in F6Publishing: 7]  [Article Influence: 2.8]  [Reference Citation Analysis (0)]
69.  Epstein BE, Schaffer DV. Combining Engineered Nucleases with Adeno-associated Viral Vectors for Therapeutic Gene Editing. Adv Exp Med Biol. 2017;1016:29-42.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 8]  [Cited by in F6Publishing: 3]  [Article Influence: 2.7]  [Reference Citation Analysis (0)]
70.  U. S. Food and Drug Administration. Fact Sheet for Healthcare Providers Administering Vaccine (Vaccination Providers): emergency use authorization (EUA) of the Janssen COVID-19 vaccine. [cited 10 December 2020].  In: U.S. Food and Drug Administration [Internet]. Available from:  [PubMed]  [DOI]  [Cited in This Article: ]
71.  U. S. Food and Drug Administration. Joint CDC and FDA Statement on Johnson & Johnson COVID-19 Vaccine. [cited 11 December 2020].  In: U.S. Food and Drug Administration [Internet]. Available from:  [PubMed]  [DOI]  [Cited in This Article: ]
72.  U. S. Food and Drug Administration. FDA and CDC Lift Recommended Pause on Johnson & Johnson (Janssen) COVID-19 Vaccine Use Following Thorough Safety Review. [cited 11 December 2020].  In: U.S. Food and Drug Administration [Internet]. Available from:  [PubMed]  [DOI]  [Cited in This Article: ]
73.  Polack FP, Thomas SJ, Kitchin N, Absalon J, Gurtman A, Lockhart S, Perez JL, Pérez Marc G, Moreira ED, Zerbini C, Bailey R, Swanson KA, Roychoudhury S, Koury K, Li P, Kalina WV, Cooper D, Frenck RW Jr, Hammitt LL, Türeci Ö, Nell H, Schaefer A, Ünal S, Tresnan DB, Mather S, Dormitzer PR, Şahin U, Jansen KU, Gruber WC;  C4591001 Clinical Trial Group. Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. N Engl J Med. 2020;383:2603-2615.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 2642]  [Cited by in F6Publishing: 967]  [Article Influence: 2642.0]  [Reference Citation Analysis (0)]
74.  U. S. Food and Drug Administration. Fact Sheet for Healthcare Providers Administering Vaccine (Vaccination Providers): Emergency use authorization (EUA) of the Pfizer-BioNTech COVID-19 vaccine to prevent coronavirus disease 2019 (COVID-19). [cited 11 December 2020].  In: U.S. Food and Drug Administration [Internet]. Available from:  [PubMed]  [DOI]  [Cited in This Article: ]
75.  U. S. Food and Drug Administration. Pfizer-BioNTech COVID-19 Vaccine. [cited 11 December 2020].  In: U.S. Food and Drug Administration [Internet]. Available from:  [PubMed]  [DOI]  [Cited in This Article: ]
76.  Jackson LA, Anderson EJ, Rouphael NG, Roberts PC, Makhene M, Coler RN, McCullough MP, Chappell JD, Denison MR, Stevens LJ, Pruijssers AJ, McDermott A, Flach B, Doria-Rose NA, Corbett KS, Morabito KM, O'Dell S, Schmidt SD, Swanson PA 2nd, Padilla M, Mascola JR, Neuzil KM, Bennett H, Sun W, Peters E, Makowski M, Albert J, Cross K, Buchanan W, Pikaart-Tautges R, Ledgerwood JE, Graham BS, Beigel JH;  mRNA-1273 Study Group. An mRNA Vaccine against SARS-CoV-2 - Preliminary Report. N Engl J Med. 2020;383:1920-1931.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 1104]  [Cited by in F6Publishing: 431]  [Article Influence: 1104.0]  [Reference Citation Analysis (0)]
77.  U. S. Food and Drug Administration. Fact Sheet for Healthcare Providers Administering Vaccine (Vaccination Providers): Emergency use authorization (EUA) of the moderna COVID-19 vaccine to prevent coronavirus disease 2019 (COVID-19). [cited 11 December 2020].  In: U.S. Food and Drug Administration [Internet]. Available from:  [PubMed]  [DOI]  [Cited in This Article: ]
78.  U. S. Food and Drug Administration. Moderna COVID-19 Vaccine. [cited 11 December 2020].  In: U.S. Food and Drug Administration [Internet]. Available from:  [PubMed]  [DOI]  [Cited in This Article: ]
79.  Liebow A, Li X, Racie T, Hettinger J, Bettencourt BR, Najafian N, Haslett P, Fitzgerald K, Holmes RP, Erbe D, Querbes W, Knight J. An Investigational RNAi Therapeutic Targeting Glycolate Oxidase Reduces Oxalate Production in Models of Primary Hyperoxaluria. J Am Soc Nephrol. 2017;28:494-503.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 88]  [Cited by in F6Publishing: 18]  [Article Influence: 17.6]  [Reference Citation Analysis (0)]
80.  Roshmi RR, Yokota T. Viltolarsen for the treatment of Duchenne muscular dystrophy. Drugs Today (Barc). 2019;55:627-639.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 21]  [Cited by in F6Publishing: 14]  [Article Influence: 10.5]  [Reference Citation Analysis (0)]
81.  Beyar-Katz O, Gill S. Advances in chimeric antigen receptor T cells. Curr Opin Hematol. 2020;27:368-377.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 8]  [Cited by in F6Publishing: 4]  [Article Influence: 8.0]  [Reference Citation Analysis (0)]
82.  Heo YA. Golodirsen: First Approval. Drugs. 2020;80:329-333.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 62]  [Cited by in F6Publishing: 40]  [Article Influence: 62.0]  [Reference Citation Analysis (0)]
83.  Scott LJ. Givosiran: First Approval. Drugs. 2020;80:335-339.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 96]  [Cited by in F6Publishing: 53]  [Article Influence: 96.0]  [Reference Citation Analysis (0)]
84.  Hoy SM. Onasemnogene Abeparvovec: First Global Approval. Drugs. 2019;79:1255-1262.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 102]  [Cited by in F6Publishing: 46]  [Article Influence: 51.0]  [Reference Citation Analysis (0)]
85.  Benson MD, Waddington-Cruz M, Berk JL, Polydefkis M, Dyck PJ, Wang AK, Planté-Bordeneuve V, Barroso FA, Merlini G, Obici L, Scheinberg M, Brannagan TH 3rd, Litchy WJ, Whelan C, Drachman BM, Adams D, Heitner SB, Conceição I, Schmidt HH, Vita G, Campistol JM, Gamez J, Gorevic PD, Gane E, Shah AM, Solomon SD, Monia BP, Hughes SG, Kwoh TJ, McEvoy BW, Jung SW, Baker BF, Ackermann EJ, Gertz MA, Coelho T. Inotersen Treatment for Patients with Hereditary Transthyretin Amyloidosis. N Engl J Med. 2018;379:22-31.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 519]  [Cited by in F6Publishing: 99]  [Article Influence: 173.0]  [Reference Citation Analysis (0)]
86.  Riedell PA, Bishop MR. Safety and efficacy of axicabtagene ciloleucel in refractory large B-cell lymphomas. Ther Adv Hematol. 2020;11:2040620720902899.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 6]  [Cited by in F6Publishing: 4]  [Article Influence: 6.0]  [Reference Citation Analysis (0)]
87.  Maude SL, Laetsch TW, Buechner J, Rives S, Boyer M, Bittencourt H, Bader P, Verneris MR, Stefanski HE, Myers GD, Qayed M, De Moerloose B, Hiramatsu H, Schlis K, Davis KL, Martin PL, Nemecek ER, Yanik GA, Peters C, Baruchel A, Boissel N, Mechinaud F, Balduzzi A, Krueger J, June CH, Levine BL, Wood P, Taran T, Leung M, Mueller KT, Zhang Y, Sen K, Lebwohl D, Pulsipher MA, Grupp SA. Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia. N Engl J Med. 2018;378:439-448.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 1766]  [Cited by in F6Publishing: 501]  [Article Influence: 588.7]  [Reference Citation Analysis (0)]
88.  Chiriboga CA. Nusinersen for the treatment of spinal muscular atrophy. Expert Rev Neurother. 2017;17:955-962.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 49]  [Cited by in F6Publishing: 26]  [Article Influence: 12.3]  [Reference Citation Analysis (0)]
89.  Lim KR, Maruyama R, Yokota T. Eteplirsen in the treatment of Duchenne muscular dystrophy. Drug Des Devel Ther. 2017;11:533-545.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 191]  [Cited by in F6Publishing: 57]  [Article Influence: 47.8]  [Reference Citation Analysis (0)]
90.  Bommareddy PK, Patel A, Hossain S, Kaufman HL. Talimogene Laherparepvec (T-VEC) and Other Oncolytic Viruses for the Treatment of Melanoma. Am J Clin Dermatol. 2017;18:1-15.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 99]  [Cited by in F6Publishing: 49]  [Article Influence: 24.8]  [Reference Citation Analysis (0)]
91.  Business Wire  Pfizer and Sangamo Announce Updated Phase 1/2 Results Showing Sustained Factor VIII Activity Levels and No Bleeding Events or Factor Usage in 3e13 vg/kg Cohort Following giroctocogene fitelparvovec (SB-525) Gene Therapy. [cited 10 December 2020]. In: Business Wire: Berkshire Hathaway Company. Available from:  [PubMed]  [DOI]  [Cited in This Article: ]
92.  Brandts J, Ray KK. Clinical implications and outcomes of the ORION Phase III trials. Future Cardiol. 2020;.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 2]  [Cited by in F6Publishing: 2]  [Article Influence: 2.0]  [Reference Citation Analysis (0)]
93.  Witztum JL, Gaudet D, Freedman SD, Alexander VJ, Digenio A, Williams KR, Yang Q, Hughes SG, Geary RS, Arca M, Stroes ESG, Bergeron J, Soran H, Civeira F, Hemphill L, Tsimikas S, Blom DJ, O'Dea L, Bruckert E. Volanesorsen and Triglyceride Levels in Familial Chylomicronemia Syndrome. N Engl J Med. 2019;381:531-542.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 144]  [Cited by in F6Publishing: 22]  [Article Influence: 72.0]  [Reference Citation Analysis (0)]
94.  Frangoul H, Altshuler D, Cappellini MD, Chen YS, Domm J, Eustace BK, Foell J, de la Fuente J, Grupp S, Handgretinger R, Ho TW, Kattamis A, Kernytsky A, Lekstrom-Himes J, Li AM, Locatelli F, Mapara MY, de Montalembert M, Rondelli D, Sharma A, Sheth S, Soni S, Steinberg MH, Wall D, Yen A, Corbacioglu S. CRISPR-Cas9 Gene Editing for Sickle Cell Disease and β-Thalassemia. N Engl J Med. 2021;384:252-260.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 120]  [Cited by in F6Publishing: 47]  [Article Influence: 120.0]  [Reference Citation Analysis (0)]