Definition and research guide
This page combines a MeSH definition, publication statistics and selected research abstracts. It is a starting point for reading the literature, not a medical textbook or a systematic evidence review.
Content available: 4 complete abstracts (611 words), 10 references. Full article text is not stored or reproduced here; follow the PMID, DOI or PMC links to read the original sources and their access terms.
Definition
The integration of exogenous DNA into the genome of an organism at sites where its expression can be suitably controlled. This integration occurs as a result of homologous recombination.
Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.
Also known as: Gene Targetings; Targeting, Gene; Targetings, Gene.
Where it fits in the MeSH classification
- Broader topics
- Genetic Techniques
- Narrower topics
- Gene Knock-In Techniques; Gene Knockdown Techniques; Gene Knockout Techniques
Research landscape
PubMed indexes 62,434 records tagged with the MeSH heading “Gene Targeting” (counts retrieved 2026-10-29). 12,385 of them (19.8%) were published from 2020 onward, and the busiest period so far is 2010-2019 with 41,293 records.
Reviews account for 2,804 records (4.5%) and meta-analyses for 28. Randomized controlled trials number 9 (0.0%) as a share of all records on the topic. Randomized trials make up only a small share of this literature, so much of what is known comes from laboratory, observational or descriptive work.
Show the data
| Period | Records |
|---|---|
| through 1999 | 834 |
| 2000-2009 | 7,922 |
| 2010-2019 | 41,293 |
| 2020 onward | 12,385 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 2,804 | 4.5% |
| Meta-analyses | 28 | 0.0% |
| Randomized controlled trials | 9 | 0.0% |
Method: PubMed query "Gene Targeting"[MeSH Terms] with publication-type and date filters, retrieved 2026-10-29.
Reading the evidence in genetics and genomics
Genetic findings vary widely in strength. A variant linked to a condition in one study may not replicate in other ancestries, and most common variants have small effects that are meaningful only in aggregate. Studies of rare, high-impact variants can support strong causal claims about a gene, while association studies describe statistical links that need functional and independent replication. Check the sample size, the ancestry of participants, whether results were replicated, and whether a laboratory or clinical outcome was actually measured.
Evidence from open-access studies
These open-access studies come from PubMed’s best-match results for this heading (papers whose main topic it is), ranked here by citation count, with one recent addition. Each abstract is reproduced in full under its recorded open licence so that you can read the authors’ own words. They illustrate the literature; they are not a systematic summary of it. Citation counts measure attention, not reliability or clinical benefit.
| Study / authors | Year | Source label / design | Europe PMC citations | Licence / source |
|---|---|---|---|---|
| Targeting circular RNAs as a therapeutic approach: current strategies and challenges | 2021 | Review article Design not recorded in structured metadata | 460 | cc by PMID 34016945 · DOI · PMC8137869 |
| Exosome-mediated delivery of CRISPR/Cas9 for targeting of oncogenic KrasG12D in pancreatic cancer | 2021 | Research article Design not recorded in structured metadata | 169 | cc by PMID 34282051 · DOI · PMC8321670 |
| Efficient gene knockout and genetic interaction screening using the in4mer CRISPR/Cas12a multiplex knockout platform | 2024 | Research article Design not recorded in structured metadata | 78 | cc by PMID 38678031 · DOI · PMC11055879 |
| Improved in vivo gene knockout with high specificity using multiplexed Cas12a sgRNAs | 2026 | Research article Design not recorded in structured metadata | 4 | cc by PMID 41540063 · DOI · PMC12827956 |
Targeting circular RNAs as a therapeutic approach: current strategies and challenges [1]
Abstract reading summary — source excerpts
- Opening excerpt
- Significant progress has been made in circular RNA (circRNA) research in recent years.
- Closing excerpt
- Lastly, we discuss major challenges and propose future directions for the development of circRNA-based therapeutics.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (177 words)
Significant progress has been made in circular RNA (circRNA) research in recent years. Increasing evidence suggests that circRNAs play important roles in many cellular processes, and their dysregulation is implicated in the pathogenesis of various diseases. CircRNAs are highly stable and usually expressed in a tissue- or cell type-specific manner. Therefore, they are currently being explored as potential therapeutic targets. Gain-of-function and loss-of-function approaches are typically performed using circRNA expression plasmids and RNA interference-based strategies, respectively. These strategies have limitations that can be mitigated using nanoparticle and exosome delivery systems. Furthermore, recent developments show that the cre-lox system can be used to knockdown circRNAs in a cell-specific manner. While still in the early stages of development, the CRISPR/Cas13 system has shown promise in knocking down circRNAs with high specificity and efficiency. In this review, we describe circRNA properties and functions and highlight their significance in disease. We summarize strategies that can be used to overexpress or knockdown circRNAs as a therapeutic approach. Lastly, we discuss major challenges and propose future directions for the development of circRNA-based therapeutics.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 34016945 · DOI · PMC8137869
Exosome-mediated delivery of CRISPR/Cas9 for targeting of oncogenic KrasG12D in pancreatic cancer [2]
Abstract reading summary — source excerpts
- Opening excerpt
- CRISPR/Cas9 is a promising technology for gene editing.
- Closing excerpt
- Exosomes may thus be a promising delivery platform for CRISPR/Cas9 gene editing for targeted therapies.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (122 words)
CRISPR/Cas9 is a promising technology for gene editing. To date, intracellular delivery vehicles for CRISPR/Cas9 are limited by issues of immunogenicity, restricted packaging capacity, and low tolerance. Here, we report an alternative, nonviral delivery system for CRISPR/Cas9 based on engineered exosomes. We show that non-autologous exosomes can encapsulate CRISPR/Cas9 plasmid DNA via commonly available transfection reagents and can be delivered to recipient cancer cells to induce targeted gene deletion. As a proof-of-principle, we demonstrate that exosomes loaded with CRISPR/Cas9 can target the mutant Kras G12D oncogenic allele in pancreatic cancer cells to suppress proliferation and inhibit tumor growth in syngeneic subcutaneous and orthotopic models of pancreatic cancer. Exosomes may thus be a promising delivery platform for CRISPR/Cas9 gene editing for targeted therapies.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 34282051 · DOI · PMC8321670
Efficient gene knockout and genetic interaction screening using the in4mer CRISPR/Cas12a multiplex knockout platform [3]
Abstract reading summary — source excerpts
- Opening excerpt
- Genetic interactions mediate the emergence of phenotype from genotype, but technologies for combinatorial genetic perturbation in mammalian cells are challenging to scale.
- Closing excerpt
- Importantly, the in4mer platform offers a fivefold reduction in library size compared to other genetic interaction methods, substantially reducing the cost and effort required for these assays.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (150 words)
Genetic interactions mediate the emergence of phenotype from genotype, but technologies for combinatorial genetic perturbation in mammalian cells are challenging to scale. Here, we identify background-independent paralog synthetic lethals from previous CRISPR genetic interaction screens, and find that the Cas12a platform provides superior sensitivity and assay replicability. We develop the in4mer Cas12a platform that uses arrays of four independent guide RNAs targeting the same or different genes. We construct a genome-scale library, Inzolia, that is ~30% smaller than a typical CRISPR/Cas9 library while also targeting ~4000 paralog pairs. Screens in cancer cells demonstrate discrimination of core and context-dependent essential genes similar to that of CRISPR/Cas9 libraries, as well as detection of synthetic lethal and masking/buffering genetic interactions between paralogs of various family sizes. Importantly, the in4mer platform offers a fivefold reduction in library size compared to other genetic interaction methods, substantially reducing the cost and effort required for these assays.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 38678031 · DOI · PMC11055879
Improved in vivo gene knockout with high specificity using multiplexed Cas12a sgRNAs [4]
Abstract reading summary — source excerpts
- Opening excerpt
- CRISPR nuclease-mediated gene knock-out is limited by suboptimal sgRNAs, inaccessible target sites, and undesired repair outcomes.
- Closing excerpt
- The system described here provides a framework for reliable gene knock-out in multicellular systems.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (162 words)
CRISPR nuclease-mediated gene knock-out is limited by suboptimal sgRNAs, inaccessible target sites, and undesired repair outcomes. Here, we present a Cas12a-based system in Drosophila that targets each gene with four sgRNAs to overcome these limitations. Multiplexed sgRNAs act through redundancy and synergism, frequently creating deletions between target sites and increasing the fraction of loss-of-function mutations. We show that multiplexed gene targeting is well tolerated and does not cause widespread proximity effects. To visualize CRISPR-nuclease activity in living animals, we developed a screening assay and used it to assess Cas12a activity across 33% of the Drosophila genome in combination with over 2000 sgRNAs. This revealed remarkably high on-target (>99%) and very low (<1%) off-target activity of multiplexed Cas12a sgRNA arrays. Quantitative side-by-side comparisons with current Cas9-based systems targeting over 100 genes in parallel demonstrate that multiplexed Cas12a gene targeting achieves superior performance and reveals phenotypes missed by established methods. The system described here provides a framework for reliable gene knock-out in multicellular systems.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 41540063 · DOI · PMC12827956
Key reviews and meta-analyses
The most cited review-type papers among PubMed’s best-match results for this heading, listed with bibliographic details only. Follow the links for the full text and access terms.
- Research article Development and applications of CRISPR-Cas9 for genome engineering [5]
- Research article Target-enrichment strategies for next-generation sequencing [6]
- Research article Genetic compensation: A phenomenon in search of mechanisms [7]
- Research article Targeting long non-coding RNA to therapeutically upregulate gene expression [8]
- Research article Sp1 transcription factor: A long-standing target in cancer chemotherapy [9]
- Research article Therapeutic AAV Gene Transfer to the Nervous System: A Clinical Reality [10]
References
- He AT, Liu J, Li F, Yang BB. Targeting circular RNAs as a therapeutic approach: current strategies and challenges. . 2021. PMID 34016945 · DOI · PMC8137869
- McAndrews KM, Xiao F, Chronopoulos A, LeBleu VS, Kugeratski FG, Kalluri R. Exosome-mediated delivery of CRISPR/Cas9 for targeting of oncogenic KrasG12D in pancreatic cancer. . 2021. PMID 34282051 · DOI · PMC8321670
- Esmaeili Anvar N, Lin C, Ma X, Wilson LL, Steger R, Sangree AK, et al.. Efficient gene knockout and genetic interaction screening using the in4mer CRISPR/Cas12a multiplex knockout platform. . 2024. PMID 38678031 · DOI · PMC11055879
- Port F, Buhmann MA, Zhou J, Stricker M, Vaughan-Brown A, Michalsen AC, et al.. Improved in vivo gene knockout with high specificity using multiplexed Cas12a sgRNAs. . 2026. PMID 41540063 · DOI · PMC12827956
- Hsu PD, Lander ES, Zhang F. Development and applications of CRISPR-Cas9 for genome engineering. Cell. 2014. PMID 24906146 · DOI · PMC4343198
- Mamanova L, Coffey AJ, Scott CE, Kozarewa I, Turner EH, Kumar A, et al.. Target-enrichment strategies for next-generation sequencing. Nat Methods. 2010. PMID 20111037 · DOI
- El-Brolosy MA, Stainier DYR. Genetic compensation: A phenomenon in search of mechanisms. PLoS Genet. 2017. PMID 28704371 · DOI · PMC5509088
- Wahlestedt C. Targeting long non-coding RNA to therapeutically upregulate gene expression. Nat Rev Drug Discov. 2013. PMID 23722346 · DOI
- Vizcaíno C, Mansilla S, Portugal J. Sp1 transcription factor: A long-standing target in cancer chemotherapy. Pharmacol Ther. 2015. PMID 25960131 · DOI
- Hudry E, Vandenberghe LH. Therapeutic AAV Gene Transfer to the Nervous System: A Clinical Reality. Neuron. 2019. PMID 30844402 · DOI · PMC11804970
About this article
- Sources
- NLM Medical Subject Headings (definition, synonyms); NCBI PubMed (counts, identifiers); Europe PMC (open-access abstracts and citation counts).
- Verification
- Every reference was resolved against PubMed on 2026-10-31; title, year and DOI matched.
- Review state
- automated source verified; no human expert review has been recorded yet.
- Version
- 1, last updated 2026-10-29.
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Evidence strength
EvidenceHelix's computed view of the study designs behind this topic: how common meta-analyses, randomized trials and reviews are, how recent the literature is, and a plain-language reading. It describes the design mix of the literature. It is not a quality appraisal of any study, and it is not medical advice.