Kotterman, M. A. & Schaffer, D. V. Engineering adeno-associated viruses for clinical gene therapy. Nat. Rev. Genet. 15, 445–451 (2014).
Keeler, A. M. & Flotte, T. R. Recombinant adeno-associated virus gene therapy in light of Luxturna (and Zolgensma and Glybera): where are we, and how did we get here? Annu. Rev. Virol. 6, 601–621 (2019).
Google Scholar
Wang, L., Wang, H., Bell, P., Mcmenamin, D. & Wilson, J. M. Brief report hepatic gene transfer in neonatal mice by adeno-associated virus serotype 8 vector. Hum. Gene Ther. 23, 533–539 (2011).
Wang, L. et al. AAV8-mediated hepatic gene transfer in infant rhesus monkeys (Macaca mulatta). Mol. Ther. 19, 2012–2020 (2012).
Cunningham, S. C., Dane, A. P., Spinoulas, A. & Alexander, I. E. Gene delivery to the juvenile mouse liver using AAV2/8 vectors. Mol. Ther. 16, 1081–1088 (2008).
Google Scholar
Barzel, A. et al. Promoterless gene targeting without nucleases ameliorates haemophilia B in mice. Nature 517, 360–364 (2015).
Google Scholar
Porro, F. et al. Promoterless gene targeting without nucleases rescues lethality of a Crigler–Najjar syndrome mouse model. EMBO Mol. Med. 9, 1346–1355 (2017).
Google Scholar
Hösel, M. et al. Autophagy determines efficiency of liver-directed gene therapy with adeno-associated viral vectors. Hepatology 66, 252–265 (2017).
Google Scholar
Schreiber, C. A. et al. An siRNA screen identifies the U2 snRNP spliceosome as a host restriction factor for recombinant adeno-associated viruses. PLoS Pathog. 11, e1005082 (2015).
Google Scholar
Johnson, J. S. & Samulski, R. J. Enhancement of adeno-associated virus infection by mobilizing capsids into and out of the nucleolus. J. Virol. 83, 2632–2644 (2009).
Google Scholar
Kia, A., Yata, T., Hajji, N. & Hajitou, A. Inhibition of histone deacetylation and DNA methylation improves gene expression mediated by the adeno-associated virus/phage in cancer cells. Viruses 5, 2561–2572 (2013).
Google Scholar
Okada, T. et al. A histone deacetylase inhibitor enhances recombinant adeno-associated virus-mediated gene expression in tumor cells. Mol. Ther. 13, 738–746 (2006).
Google Scholar
Russell, D. W., Alexander, I. E. & Miller, A. D. DNA synthesis and topoisomerase inhibitors increase transduction by adeno-associated virus vectors. Proc. Natl Acad. Sci. USA 92, 5719–5723 (1995).
Google Scholar
Nicolson, S. C., Li, C., Hirsch, M. L., Setola, V. & Samulski, R. J. Identification and validation of small molecules that enhance recombinant adeno-associated virus transduction following high-throughput screens. J. Virol. 90, 7019–7031 (2016).
Google Scholar
Zhong, L. et al. Heat-shock treatment-mediated increase in transduction by recombinant adeno-associated virus 2 vectors is independent of the cellular heat-shock protein 90. J. Biol. Chem. 279, 12714–12723 (2004).
Google Scholar
Marcus-Sekura, C. J. & Carter, B. J. Chromatin-like structure of adeno-associated virus DNA in infected cells. J. Virol. 48, 79–87 (1983).
Google Scholar
de Alencastro, G. et al. Improved genome editing through inhibition of FANCM and members of the BTR dissolvase complex. Mol. Ther. 29.3, 1016–1027 (2021).
Aye, Y., Li, M., Long, M. J. C. & Weiss, R. S. Ribonucleotide reductase and cancer: biological mechanisms and targeted therapies. Oncogene 34, 2011–2021 (2015).
Google Scholar
De Caneva, A. et al. Coupling AAV-mediated promoterless gene targeting to SaCas9 nuclease to efficiently correct liver metabolic diseases. JCI Insight 5, e128863. (2019).
Maurer-Schultze, B., Siebert, M. & Bassukas, I. D. An in vivo study on the synchronizing effect of hydroxyurea. Exp. Cell. Res. 174, 230–243 (1988).
Google Scholar
Wongt, E. A. & Capecchi, M. R. Homologous recombination between coinjected DNA sequences peaks in early to mid-S phase. Mol. Cell Biol. 7, 2294–2295 (1987).
Rothkamm, K., Krüger, I., Thompson, L. H., Löbrich, M. & Biophysik, F. Pathways of DNA double-strand break repair during the mammalian cell cycle the induction and repair of individual IR-induced DSBs. Mol. Cell. Biol. 23, 5706–5715 (2003).
Google Scholar
Heyer, W.-D., Ehmsen, K. T. & Liu, J. Regulation of homologous recombination in eukaryotes. Annu. Rev. Genet. 44, 113–139 (2010).
Google Scholar
Sandoval, A., Consoli, U., Plunkett, W. & Anderson, M. D. Fludarabine-mediated inhibition of nucleotide excision repair induces apoptosis in quiescent human lymphocytes. Clin. Cancer Res. 2, 1731–1741 (1996).
Google Scholar
Huang, P., Chubb, S. & Plunketts, W. Termination of DNA synthesis by 9-β-d-arabinofuranosyl-2-fluoroadenine. A mechanism for cytotoxicity. J. Biol. Chem. 265, 16617–16625 (1990).
Huang, P., Sandoval, A., Van Den Neste, E., Keating, M. J. & Plunkett, W. Inhibition of RNA transcription: a biochemical mechanism of action against chronic lymphocytic leukemia cells by fludarabine. Leukemia 14, 1405–1413 (2000).
Pettitt, A. R. Mechanism of action of purine analogues in chronic lymphocytic leukaemia. Br. J. Haematol. 121, 692–702 (2003).
Google Scholar
Tseng, W. C., Derse, D., Cheng, Y. C., Brockman, R. W. & Bennett, L. L. In vitro biological activity of 9-β-d-arabinofuranosyl-2-fluoroadenine and the biochemical actions of its triphosphate on DNA polymerases and ribonucleotide reductase from HeLa cells. Mol. Pharmacol. 21, 474–477 (1982).
Lans, H., Hoeijmakers, J. H. J., Vermeulen, W. & Marteijn, J. A. The DNA damage response to transcription stress. Nat. Rev. Mol. Cell Biol. 20, 766–784 (2019).
Google Scholar
Yasuhara, T. et al. Human Rad52 promotes XPG-mediated R-loop processing to initiate transcription-associated homologous recombination repair. Cell 175, 558–570 (2018).
Google Scholar
Stoimenov, I., Gottipati, P., Schultz, N. & Helleday, T. Transcription inhibition by 5,6-dichloro-1-β-d-ribofuranosylbenzimidazole (DRB) causes DNA damage and triggers homologous recombination repair in mammalian cells. Mutat. Res. 706, 1–6 (2011).
Google Scholar
Stiff, T. et al. ATM and DNA-PK function redundantly to phosphorylate H2AX after exposure to ionizing radiation. Cancer Res. 64, 2390–2396 (2004).
Google Scholar
Den Engelse, L. & Philippus, E. J. In vivo repair of rat liver DNA damaged by dimethylnitrosamine or diethylnitrosamine. Chem. Biol. Interact. 19, 111–124 (1977).
Ferrara, L., Parekh-Olmedo, H. & Kmiec, E. B. Enhanced oligonucleotide-directed gene targeting in mammalian cells following treatment with DNA damaging agents. Exp. Cell. Res. 300, 170–179 (2004).
Google Scholar
Porteus, M. H., Cathomen, T., Weitzman, M. D. & Baltimore, D. Efficient gene targeting mediated by adeno-associated virus and DNA double-strand breaks. Mol. Cell. Biol. 23, 3558–3565 (2003).
Google Scholar
Sentmanat, M. F., Peters, S. T., Florian, C. P., Connelly, J. P. & Pruett-Miller, S. M. A survey of validation strategies for CRISPR–Cas9 editing. Sci. Rep. 8, 888 (2018).
Google Scholar
Ju, H. Y., et al. Pharmacokinetics of fludarabine in pediatric hematopoietic stem cell transplantation. Blood 124, 2466–2466 (2014).
Maruyama, T. et al. Increasing the efficiency of precise genome editing with CRISPR–Cas9 by inhibition of nonhomologous end joining. Nat. Biotechnol. 33, 538–542 (2015).
Google Scholar
Lin, S., Staahl, B. T., Alla, R. K. & Doudna, J. A. Enhanced homology-directed human genome engineering by controlled timing of CRISPR/Cas9 delivery. eLife 3, e04766 (2014).
Yu, C. et al. Small molecules enhance CRISPR genome editing in pluripotent stem cells. Cell Stem Cell 16.2, 142–147 (2015).
Vasileva, A., Linden, R. M. & Jessberger, R. Homologous recombination is required for AAV-mediated gene targeting. Nucleic Acids Res. 34, 3345–3360 (2006).
Google Scholar
Song, J. et al. RS-1 enhances CRISPR/Cas9-and TALEN-mediated knock-in efficiency. Nat. Commun. 7, 10548 (2016).
Google Scholar
Zhang, W. et al. A high-throughput small molecule screen identifies farrerol as a potentiator of CRISPR/Cas9-mediated genome editing. eLife 9, e56008 (2020).
Google Scholar
Zhao, T. et al. Small-molecule compounds boost genome-editing efficiency of cytosine base editor. Nucleic Acids Res. 49, 8974–8986 (2021).
Google Scholar
Chandler, R. J. et al. Vector design influences hepatic genotoxicity after adeno-associated virus gene therapy. J. Clin. Invest. 125, 870–880 (2015).
Google Scholar
Montini, E. et al. The genotoxic potential of retroviral vectors is strongly modulated by vector design and integration site selection in a mouse model of HSC gene therapy. J. Clin. Invest. 119, 964–975 (2009).
Google Scholar
Chandler, R. J. et al. Promoterless, nuclease‐free genome editing confers a growth advantage for corrected hepatocytes in mice with methylmalonic acidemia. Hepatology 73, 2223–2237 (2021).
Google Scholar
Trobridge, G., Hirata, R. K. & Russell, D. W. Gene targeting by adeno-associated virus vectors is cell-cycle dependent. Hum. Gene Ther. 16, 522–526 (2005).
Google Scholar
Kohama, Y. et al. Adeno-associated virus-mediated gene delivery promotes S-phase entry-independent precise targeted integration in cardiomyocytes. Sci. Rep. 10, 15348 (2020).
Google Scholar
Huang, P. & Plunkett, W. Action of 9-β-d-arabinofuranosyl-2-fluoroadenine on RNA metabolism. Mol. Pharmacol. 39, 449–455 (1991).
Mailand, N. et al. RNF8 ubiquitylates histones at DNA double-strand breaks and promotes assembly of repair proteins. Cell 131, 887–900 (2007).
Google Scholar
Ji, J. H. et al. De novo phosphorylation of H2AX by WSTF regulates transcription-coupled homologous recombination repair. Nucleic Acids Res. 47, 6299–6314 (2019).
Google Scholar
Mano, M., Ippodrino, R., Zentilin, L., Zacchigna, S. & Giacca, M. Genome-wide RNAi screening identifies host restriction factors critical for in vivo AAV transduction. Proc. Natl Acad. Sci. USA 112, 11276–11281 (2015).
Cervelli, T. et al. Processing of recombinant AAV genomes occurs in specific nuclear structures that overlap with foci of DNA-damage-response proteins. J. Cell Sci. 121, 349–357 (2008).
Google Scholar
Pekrun, K. et al. Using a barcoded AAV capsid library to select for clinically relevant gene therapy vectors. JCI Insight 4, e131610 (2019).
Google Scholar
Lu, J. et al. A 5′ noncoding exon containing engineered intron enhances transgene expression from recombinant AAV vectors in vivo. Hum. Gene Ther. 28, 125–134 (2017).
Google Scholar
Grimm, D., Pandey, K., Nakai, H., Storm, T. A. & Kay, M. A. Liver transduction with recombinant adeno-associated virus is primarily restricted by capsid serotype not vector genotype. J. Virol. 80, 426–439 (2006).
Google Scholar
