Adeno-associated virus inverted terminal repeats stimulate gene editing
Open accessAbstract
Advancements in genome editing have relied on technologies to specifically damage DNA which, in turn, stimulates DNA repair including homologous recombination (HR). As off-target concerns complicate the therapeutic translation of site-specific DNA endonucleases, an alternative strategy to stimulate gene editing based on fragile DNA was investigated. To do this, an episomal gene-editing reporter was generated by a disruptive insertion of the adeno-associated virus (AAV) inverted terminal repeat (ITR) into the egfp gene. Compared with a non-structured DNA control sequence, the ITR induced DNA damage as evidenced by increased gamma-H2AX and Mre11 foci formation. As local DNA damage stimulates HR, ITR-mediated gene editing was investigated using DNA oligonucleotides as repair substrates. The AAV ITR stimulated gene editing >1000-fold in a replication-independent manner and was not biased by the polarity of the repair oligonucleotide. Analysis of additional human DNA sequences demonstrated stimulation of gene editing to varying degrees. In particular, inverted yet not direct, Alu repeats induced gene editing, suggesting a role for DNA structure in the repair event. Collectively, the results demonstrate that inverted DNA repeats stimulate gene editing via double-strand break repair in an episomal context and allude to efficient gene editing of the human chromosome using fragile DNA sequences.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
A defective eGFP reporter plasmid in dividing cells was rescued (gene-edited) by adding only the ITR2-eGFPpart(165 bp)-ITR2 with 40 bp eGFP homology arms adjacent to the ITR2.
“A defective eGFP reporter plasmid in dividing cells was rescued (gene-edited) by adding only the ITR2-eGFPpart(165 bp)-ITR2 with 40 bp eGFP homology arms adjacent to the ITR2 [252].”
From Recombinant Adeno-Associated Viral Vectors (rAAV)-Vector Elements in Ocular Gene Therapy Clinical Trials and Transgene Expression and Bioactivity Assays (2020) · cites this paper as [252]
The Results and Discussion (Figure 3b; page not available in our copy) report repair of a defective eGFP plasmid reporter in human 293 cells using 40-nucleotide eGFP homology sequences. But the 165-nucleotide AAV2-ITR was inserted into the reporter plasmid, and repair required co-transfection with a separate single-stranded eGFP oligonucleotide. The paper does not describe rescuing the reporter by adding only an ITR-flanked eGFP fragment. (LLM, conf=0.88)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139
Rogakou, E. P., Pilch, D. R., Orr, A. H., Ivanova, V. S., & Bonner, W. M. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.10.5858 · Cited by 5,438 · see citing works
The double-strand-break repair model for recombination
Szostak, J. W., Orr-Weaver, T. L., Rothstein, R. J., & Stahl, F. W. (1983) · Cell · doi:10.1016/0092-8674(83)90331-8 · Cited by 2,437 · see citing works
Altering the Genome by Homologous Recombination
Capecchi, M. R. (1989) · Science · doi:10.1126/science.2660260 · Cited by 2,037 · see citing works
DNA Topoisomerases and Their Poisoning by Anticancer and Antibacterial Drugs
Pommier, Y. G., Leo, E., Zhang, H., & Marchand, C. (2010) · Chemistry & Biology · doi:10.1016/j.chembiol.2010.04.012 · Cited by 1,842 · see citing works
Chimeric nucleases stimulate gene targeting in human cells
Porteus, M. H., & Baltimore, D. (2003) · Science · doi:10.1126/science.1078395 · Cited by 741 · see citing works
The MRE11 complex: starting from the ends
Stracker, T. H., & Petrini, J. H. J. (2011) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3047 · Cited by 734 · see citing works
Gene targeting using zinc finger nucleases
Porteus, M. H., & Carroll, D. (2005) · Nature Biotechnology · doi:10.1038/nbt1125 · Cited by 641 · see citing works
Lin, Y., Cradick, T. J., Brown, M. T., Deshmukh, H., Ranjan, P., Sarode, N., Wile, B. M., Vertino, P. M., Stewart, F. J., & Bao, G. (2014) · Nucleic Acids Research · doi:10.1093/nar/gku402 · Cited by 634 · see citing works
Production and characterization of adeno-associated viral vectors
Grieger, J. C., Choi, V. W., & Samulski, R. J. (2006) · Nature Protocols · doi:10.1038/nprot.2006.207 · Cited by 567 · see citing works
An unbiased genome-wide analysis of zinc-finger nuclease specificity
Gabriel, R., Lombardo, A., Arens, A., Miller, J. C., Genovese, P., Kaeppel, C., Nowrouzi, A., Bartholomae, C. C., Wang, J., Friedman, G., et al. (2011) · Nature Biotechnology · doi:10.1038/nbt.1948 · Cited by 526 · see citing works
Revealing off-target cleavage specificities of zinc-finger nucleases by in vitro selection
Pattanayak, V., Ramirez, C. L., Joung, J. K., & Liu, D. R. (2011) · Nature Methods · doi:10.1038/nmeth.1670 · Cited by 453 · see citing works
Pathways of mammalian replication fork restart
Petermann, E., & Helleday, T. (2010) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2974 · Cited by 340 · see citing works
The cellular response to DNA double-strand breaks: defining the sensors and mediators
Petrini, J. (2003) · Trends in Cell Biology · doi:10.1016/s0962-8924(03)00170-3 · Cited by 339 · see citing works
In vivo site-directed mutagenesis using oligonucleotides
Storici, F., Lewis, L. K., & Resnick, M. A. (2001) · Nature Biotechnology · doi:10.1038/90837 · Cited by 330 · see citing works
A combinatorial approach to create artificial homing endonucleases cleaving chosen sequences
Smith, J. N. P., Grizot, S., Arnould, S., Duclert, A., Epinat, J.-C., Chames, P., Prìeto, J., Redondo, P. N., Blanco, F. J., Bravo, J., et al. (2006) · Nucleic Acids Research · doi:10.1093/nar/gkl720 · Cited by 329 · see citing works
Multiple pathways process stalled replication forks
Michel, B., Grompone, G., Florès, M.-J., & Bidnenko, V. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0401586101 · Cited by 322 · see citing works
Samulski, R. J., Srivastava, A., Berns, K. I., & Muzyczka, N. (1983) · Cell · doi:10.1016/0092-8674(83)90342-2 · Cited by 297 · see citing works
Altering Genes in Animals by Gene Targeting
Koller, B. H., & Smithies, O. (1992) · Annual Review of Immunology · doi:10.1146/annurev.iy.10.040192.003421 · Cited by 222 · see citing works
Inverted DNA Repeats: a Source of Eukaryotic Genomic Instability
Gordenin, D. A., Lobachev, K. S., Degtyareva, N. P., Malkova, A., Perkins, E. L., & Resnick, M. A. (1993) · Molecular and Cellular Biology · doi:10.1128/mcb.13.9.5315-5322.1993 · Cited by 195 · see citing works
Triplex forming oligonucleotides: sequence-specific tools for gene targeting
Knauert, M. P. (2001) · Human Molecular Genetics · doi:10.1093/hmg/10.20.2243 · Cited by 181 · see citing works
Storici, F., Durham, C. L., Gordenin, D. A., & Resnick, M. A. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2036296100 · Cited by 180 · see citing works
Efficient Gene Targeting Mediated by Adeno-Associated Virus and DNA Double-Strand Breaks
Porteus, M. H., Cathomen, T., Weitzman, M. D., & Baltimore, D. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.10.3558-3565.2003 · Cited by 159 · see citing works
Palindrome Resolution and Recombination in the Mammalian Germ Line
Akgün, E., Zahn, J. D., Baumes, S. A., Brown, G., Liang, F., Romanienko, P. J., Lewis, S. M., & Jasin, M. (1997) · Molecular and Cellular Biology · doi:10.1128/mcb.17.9.5559 · Cited by 157 · see citing works
Xiao, X., Xiao, W., Li, J., & Samulski, R. J. (1997) · Journal of Virology · doi:10.1128/jvi.71.2.941-948.1997 · Cited by 154 · see citing works
Host Cell DNA Repair Pathways in Adeno-Associated Viral Genome Processing
Choi, V. W., McCarty, D. M., & Samulski, R. J. (2006) · Journal of Virology · doi:10.1128/jvi.00841-06 · Cited by 144 · see citing works
Inverted Alu repeats unstable in yeast are excluded from the human genome
Lobachev, K. S., Stenger, J. E., Kozyreva, O. G., Jurka, J., Gordenin, D. A., & Resnick, M. A. (2000) · The EMBO Journal · doi:10.1093/emboj/19.14.3822 · Cited by 141 · see citing works
SbcCD causes a double-strand break at a DNA palindrome in the Escherichia coli chromosome.
Eykelenboom, J. K., Blackwood, J., Okely, E. A., & Leach, D. (2008) · Molecules and Cells · doi:10.1016/j.molcel.2007.12.020 · Cited by 129 · see citing works
Collins, J. F., Volckaert, G., & Nevers, P. (1982) · Gene · doi:10.1016/0378-1119(82)90198-6 · Cited by 116 · see citing works
Schwartz, R. A., Carson, C. T., Schuberth, C., & Weitzman, M. D. (2009) · Journal of Virology · doi:10.1128/jvi.00318-09 · Cited by 115 · see citing works
Yan, Z., Zak, R., Zhang, Y., & Engelhardt, J. F. (2005) · Journal of Virology · doi:10.1128/jvi.79.1.364-379.2005 · Cited by 107 · see citing works
Hairpin- and cruciform-mediated chromosome breakage: causes and consequences in eukaryotic cells
Kirill, S. L. (2007) · Frontiers in bioscience · doi:10.2741/2381 · Cited by 107 · see citing works
Coupling endonucleases with DNA end–processing enzymes to drive gene disruption
Certo, M. T., Gwiazda, K., Kuhar, R., Sather, B. D., Curinga, G., Mandt, T., Brault, M., Lambert, A. R., Baxter, S. K., Jacoby, K., et al. (2012) · Nature Methods · doi:10.1038/nmeth.2177 · Cited by 99 · see citing works
Metzger, M. J., McConnell-Smith, A., Stoddard, B. L., & Miller, A. D. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkq826 · Cited by 85 · see citing works
Cervelli, T., Palacios, J. A., Zentilin, L., Mano, M., Schwartz, R. A., Weitzman, M. D., & Giacca, M. (2008) · Journal of Cell Science · doi:10.1242/jcs.003632 · Cited by 84 · see citing works
Local DNA Sequence Control of Deletion Formation in Escherichia coli Plasmid pBR322
Dasgupta, U., Weston-Hafer, K. A., & Berg, D. E. (1987) · Genetics · doi:10.1093/genetics/115.1.41 · Cited by 84 · see citing works
Topoisomerase IIα maintains genomic stability through decatenation G2 checkpoint signaling
Bower, J. J., Karaca, G., Zhou, Y., Simpson, D. A., Cordeiro‐Stone, M., & Kaufmann, W. K. (2010) · Oncogene · doi:10.1038/onc.2010.232 · Cited by 83 · see citing works
Repair by recombination of DNA containing a palindromic sequence
Leach, D. R. F., Okely, E. A., & Pinder, D. J. (1997) · Molecular Microbiology · doi:10.1046/j.1365-2958.1997.6071957.x · Cited by 79 · see citing works
The Role of DNA-PKcs and Artemis in Opening Viral DNA Hairpin Termini in Various Tissues in Mice
Inagaki, K., Ma, C.-R., Storm, T. A., Kay, M., & Nakai, H. (2007) · Journal of Virology · doi:10.1128/jvi.01225-07 · Cited by 76 · see citing works
Farah, J. A., Hartsuiker, E., Mizuno, K.-I., Ohta, K., & Smith, G. R. (2002) · Genetics · doi:10.1093/genetics/161.1.461 · Cited by 70 · see citing works
A CRISPR Approach to Gene Targeting
Carroll, D. (2012) · Molecular Therapy · doi:10.1038/mt.2012.171 · Cited by 66 · see citing works
Group II Intron-Based Gene Targeting Reactions in Eukaryotes
Mastroianni, M., Watanabe, K. I., White, T., Zhuang, F., Vernon, J. L., Matsuura, M., Wallingford, J. B., & Lambowitz, A. M. (2008) · PLoS ONE · doi:10.1371/journal.pone.0003121 · Cited by 50 · see citing works
Hirsch, M. L., Green, L., Porteus, M. H., & Samulski, R. J. (2010) · Gene Therapy · doi:10.1038/gt.2010.65 · Cited by 42 · see citing works
Self-citationThe replication fork's five degrees of freedom, their failure and genome rearrangements
Weinert, T. A., Kaochar, S., Jones, H., Paek, A. L., & Clark, A. (2009) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2009.10.004 · Cited by 29 · see citing works
Katz, S. S., Gimble, F. S., & Storici, F. (2014) · PLoS ONE · doi:10.1371/journal.pone.0088840 · Cited by 27 · see citing works
AAV Recombineering with Single Strand Oligonucleotides
Hirsch, M. L., Storici, F., Li, C., Choi, V. W., & Samulski, R. J. (2009) · PLoS ONE · doi:10.1371/journal.pone.0007705 · Cited by 26 · see citing works
Self-citationCreating a Novel Origin of Replication through Modulating DNA-Protein Interfaces
Hewitt, F. C., & Samulski, R. J. (2010) · PLoS ONE · doi:10.1371/journal.pone.0008850 · Cited by 14 · see citing works
Site-Specific Targeting of DNA Plasmids to Chromosome 19 Using AAV Cisand TransSequences
Young, S. M., Xiao, W., & Samulski, R. J. (2003) · Humana Press eBooks · doi:10.1385/1-59259-215-5:111 · Cited by 13 · see citing works
Stuckey, S., & Storici, F. (2014) · Methods in molecular biology · doi:10.1007/978-1-62703-761-7_20 · Cited by 4 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Wang, J., Exline, C. M., DeClercq, J. J., Llewellyn, G. N., Hayward, S. B., Li, P. W.-L., Shivak, D. A., Surosky, R. T., Gregory, P. D., Holmes, M. C., et al. (2015) · Nature Biotechnology · doi:10.1038/nbt.3408 · Cited by 261 · see citing works
Next-generation AAV vectors—Do not judge a virus (only) by its cover
Domenger, C., & Grimm, D. (2019) · Human Molecular Genetics · doi:10.1093/hmg/ddz148 · Cited by 147 · see citing works
Ferrari, S., Jacob, A., Cesana, D., Laugel, M., Beretta, S., Varesi, A., Unali, G., Conti, A., Canarutto, D., Albano, L., et al. (2022) · Cell stem cell · doi:10.1016/j.stem.2022.09.001 · Cited by 133 · see citing works
Adeno-Associated Viral Vectors in Neuroscience Research
Haggerty, D. L., Grecco, G. G., Reeves, K. C., & Atwood, B. K. (2019) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2019.11.012 · Cited by 123 · see citing works
Buck, T., & Wijnholds, J. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21124197 · Cited by 92 · see citing works
“This basic rAAV gene delivery vector can consist of two inverted terminal repeats (ITRs) of the AAV serotype 2 (ITR2), a promoter, a wild-type copy of the cDNA of the gene-of-interest, as well as other enhancers or transcript stabilizing elements, an intron, and a polyadenylation sequence (Figure 2B).”
BackgroundInfluentialGaj, T., Staahl, B. T., Rodrigues, G. M. C., Limsirichai, P., Ekman, F. K., Doudna, J. A., & Schaffer, D. V. (2017) · Nucleic Acids Research · doi:10.1093/nar/gkx154 · Cited by 89 · see citing works
Adeno-Associated Virus Genome Interactions Important for Vector Production and Transduction
Maurer, A. C., & Weitzman, M. D. (2020) · Human Gene Therapy · doi:10.1089/hum.2020.069 · Cited by 65 · see citing works
The Role of Recombinant AAV in Precise Genome Editing
Bijlani, S., Pang, K. M., Sivanandam, V., Singh, A., & Chatterjee, S. (2022) · Frontiers in Genome Editing · doi:10.3389/fgeed.2021.799722 · Cited by 58 · see citing works
Gene Editing of Hematopoietic Stem Cells: Hopes and Hurdles Toward Clinical Translation
Ferrari, S., Vavassori, V., Canarutto, D., Jacob, A., Castiello, M. C., Javed, A. O., & Genovese, P. (2021) · Frontiers in Genome Editing · doi:10.3389/fgeed.2021.618378 · Cited by 38 · see citing works
Liu, P., Li, X., Gu, J., Dong, Y., Liu, Y., Puthiyakunnon, S., & Chen, X. (2016) · Scientific Reports · doi:10.1038/srep20979 · Cited by 29 · see citing works
Allen, D. G., Weiss, L. E., Saguy, A., Rosenberg, M., Iancu, O., Matalon, O., Lee, C. M., Beider, K., Nagler, A., Shechtman, Y., et al. (2022) · The CRISPR Journal · doi:10.1089/crispr.2021.0128 · Cited by 24 · see citing works
AAV Biology, Infectivity and Therapeutic Use from Bench to Clinic
Vance, M. A., Mitchell, A. M., & Samulski, R. J. (2015) · InTech eBooks · doi:10.5772/61988 · Cited by 22 · see citing works
A Curative DNA Code for Hematopoietic Defects
Porteus, M. H., Pavel-Dinu, M., & Pai, S. (2022) · Hematology/Oncology Clinics of North America · doi:10.1016/j.hoc.2022.05.002 · Cited by 15 · see citing works
Yamamoto, H., Ishimura, M., Ochiai, M., Takada, H., Kusuhara, K., Nakatsu, Y., Tsuzuki, T., Mitani, K., & Hara, T. (2015) · Gene Therapy · doi:10.1038/gt.2015.91 · Cited by 13 · see citing works
Song, L., Hasegawa, T., Brown, N. J., Bower, J. J., Samulski, R. J., & Hirsch, M. L. (2025) · Nucleic Acids Research · doi:10.1093/nar/gkaf013 · Cited by 12 · see citing works
Self-citationBatool, K., Alam, I., Liu, P., Shu, Z., Zhao, S., Yang, W., Xiao, J., Gu, J., & Chen, X. (2022) · Toxins · doi:10.3390/toxins14020147 · Cited by 12 · see citing works
Evaluating the Genomic Parameters Governing rAAV-Mediated Homologous Recombination
Spector, L. P., Tiffany, M. R., Ferraro, N. M., Abell, N. S., Montgomery, S. B., & Kay, M. A. (2020) · Molecular Therapy · doi:10.1016/j.ymthe.2020.11.025 · Cited by 12 · see citing works
Improved Genome Editing through Inhibition of FANCM and Members of the BTR Dissolvase Complex
de Alencastro, G., Puzzo, F., Pavel-Dinu, M., Zhang, F., Pillay, S., Majzoub, K., Tiffany, M. R., Jang, H., Sheikali, A., Cromer, M. K., et al. (2020) · Molecular Therapy · doi:10.1016/j.ymthe.2020.10.020 · Cited by 11 · see citing works
Rare immune diseases paving the road for genome editing-based precision medicine
Pavel-Dinu, M., Borna, Š., & Bacchetta, R. (2023) · Frontiers in Genome Editing · doi:10.3389/fgeed.2023.1114996 · Cited by 10 · see citing works
Moço, P. D., Farnós, O., Sharon, D. M., & Kamen, A. (2023) · Current Issues in Molecular Biology · doi:10.3390/cimb45100486 · Cited by 8 · see citing works
AAVS1-Targeted Plasmid Integration in AAV Producer Cell Lines
Luo, Y., Frederick, A., Martin, J. M., Scaria, A., Cheng, S. H., Armentano, D., Wadsworth, S. C., & Vincent, K. A. (2017) · Human Gene Therapy Methods · doi:10.1089/hgtb.2016.158 · Cited by 7 · see citing works
AAV-mediated genome editing is influenced by the formation of R-loops
Puzzo, F., Crossley, M. P., Goswami, A., Zhang, F., Pekrun, K., Garzon, J. L., Cimprich, K. A., & Kay, M. A. (2024) · Molecular Therapy · doi:10.1016/j.ymthe.2024.09.035 · Cited by 4 · see citing works
Stabilization of a single-stranded DNA of adeno-associated virus by inverted terminal repeats
Yuan, Y.-Z., Higashiyama, K., Ito-Kudo, E., Masumi-Koizumi, K., Yusa, K., & Uchida, K. (2024) · Scientific Reports · doi:10.1038/s41598-024-78612-y · Cited by 5 · see citing works
Dou, D., Lu, J., Chen, X., & Zhang, X. (2025) · Pharmaceutical Research · doi:10.1007/s11095-025-03931-2 · Cited by 3 · see citing works
Li, P., Marino, M. P., Zou, J., Argaw, T., Morreale, M. T., Iaffaldano, B. J., & Reiser, J. (2018) · Human Gene Therapy Methods · doi:10.1089/hgtb.2018.052 · Cited by 3 · see citing works
Sha, Y., Yan, W., Liu, X., Chai, H., Chen, J., Li, H., Wang, M., Jiang, S., Wang, S., Ren, Y., et al. (2024) · Avian Pathology · doi:10.1080/03079457.2024.2373366 · Cited by 2 · see citing works
The Therapeutic Targeting of Long Noncoding RNA
Woo, C. J. (2017) · Topics in medicinal chemistry · doi:10.1007/7355_2017_25 · Cited by 2 · see citing works
The future of pediatric gene therapy: CRISPR-Cas9, AI, and personalized medicine
Pan, Y., Ding, J., Wang, W., Xu, D., Fan, J., & Zhang, W. (2026) · Pediatric Research · doi:10.1038/s41390-026-05270-3 · Cited by 1 · see citing works
Ou-Yang, H., Yang, S.-H., Chen, W., Yang, S., Cidem, A., Sung, L., & Chen, C. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23073973
Gupta, K., Xu, P., Gallant, J., Yoon, Y., Rivera‐Pérez, J. A., & Lawrence, J. B. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.09.29.615605
Potential effects of endogenous RNA/DNA hybrids on CRISPR-Cas9-mediated homology-directed repair
Puzzo, F., Bayram, B., Macaubas, C., Lin, A., Jang, H., Zhang, F., Mellins, E., & Kay, M. A. (2026) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2026.102880
Li, Y., Zhang, W., & Tang, D. (2026) · Current Urology · doi:10.1097/cu9.0000000000000349
- Authors
- Hirsch, M. L.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Hirsch, M L
- ORCID
- Hirsch, M L
- Venue
- Gene Therapy
- Published
- 2014-12-11
- Volume
- 22
- Issue
- 2
- Pages
- 190-195
- ISSN
- 0969-7128 (ISSN-L)
- 1476-5462
- PMC
- PMC4388141
- OpenAlex
- W1974598722
- Cited by
- 32
- References
- 48
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 4 · 2023: 2 · 2022: 6 · 2021: 1 · 2020: 4 · 2019: 2 · 2018: 1 · 2017: 3 · 2016: 1 · 2015: 3
- FWCI
- 0.96
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Gene Therapy (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- UNC Libraries
- Funders
- Research to Prevent Blindness
- Jain Foundation
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases (R01AI072176)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR064369)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Keywords
- adeno-associated virus, inverted terminal repeats, genome editing, homologous recombination, DNA double-strand break repair, Alu elements, DNA structure, off-target effects
- MeSH terms
- Dependovirus, Base Sequence, DNA Repair, Genes, Viral, Genetic Engineering, Humans, Molecular Sequence Data, Genes, Reporter, Terminal Repeat Sequences, Green Fluorescent Proteins, DNA Breaks, Double-Stranded, Inverted Repeat Sequences, HEK293 Cells
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
