{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T10:17:47Z","timestamp":1785406667179,"version":"3.56.0"},"posted":{"date-parts":[[2026,5,8]]},"group-title":"Bioengineering","reference-count":121,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T00:00:00Z","timestamp":1778198400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"award":["R01CA255064A1"],"award-info":[{"award-number":["R01CA255064A1"]}],"id":[{"id":"https:\/\/ror.org\/001d55x84","id-type":"ROR","asserted-by":"publisher"}]},{"award":["5R35GM145235"],"award-info":[{"award-number":["5R35GM145235"]}],"id":[{"id":"https:\/\/ror.org\/001d55x84","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004917","name":"Cancer Prevention and Research Institute of Texas","doi-asserted-by":"crossref","award":["RR220024"],"award-info":[{"award-number":["RR220024"]}],"id":[{"id":"10.13039\/100004917","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,5,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>The dynamic balance of cellular homeostasis is often maintained by opposing regulatory pathways, yet most genetic screens interrogate them in one direction and therefore miss the bidirectional gene-gene interactions that shape complex phenotypes such as DNA damage response (DDR). Here, we present PAIR (Parallel Activation and Interference CRISPR), a bidirectional perturbation platform that enables simultaneous activation and suppression of distinct genes within the same cell using CRISPR activation (CRISPRa) and Cas13d RNA knockdown. Applying PAIR to the CRISPR\/Cas9 induced DSB repair screen, we mapped gene-gene interactions across competing repair branches and identify synergistic perturbations, including NBN activation combined with suppression of end-joining factors, that shift repair outcomes toward homology-directed repair (HDR) and improve the precision of CRISPR-based gene editing. Using coupled PAIR with single-cell transcriptomic, we further demonstrated that NBN activation induces inflammatory and interferon programs, whereas co-suppression of end-joining factors buffers this response, revealing transcriptional states missed by conventional unidirectional perturbations. To translate these findings into non-viral chimeric antigen receptor (CAR) T cell engineering, we developed an mRNA-based strategy for parallel overexpression and knockdown of NBN-anchored DDR effectors in primary T cells, priming the T cells into a transient HDR-favored state that enhances the efficiency of CAR knock-in on the TRAC locus. Together, the PAIR system provides a general framework for studying opposing regulatory networks, uncovering hidden cell states, and guiding cell-state engineering through bidirectional perturbation.<\/jats:p>","DOI":"10.64898\/2026.05.08.722799","type":"posted-content","created":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T05:00:14Z","timestamp":1778302814000},"source":"Crossref","is-referenced-by-count":0,"title":["Parallel Activation and Interference CRISPR (PAIR) with Sequencing Uncovers DNA Repair Networks Guiding Precision Cell Engineering"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6852-1054","authenticated-orcid":false,"given":"Chen","family":"Chang","sequence":"first","affiliation":[{"name":"Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA"},{"name":"Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0535-1259","authenticated-orcid":false,"given":"Dailin","family":"Gan","sequence":"additional","affiliation":[{"name":"Department of Applied and Computational Mathematics and Statistics, University of Notre Dame, Notre Dame, South Bend, IN, 46556, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Diao","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA"},{"name":"Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Wang","sequence":"additional","affiliation":[{"name":"Cecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chantale","family":"Lacelle","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1615-0391","authenticated-orcid":false,"given":"Gary C.","family":"Hon","sequence":"additional","affiliation":[{"name":"Cecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Applied and Computational Mathematics and Statistics, University of Notre Dame, Notre Dame, South Bend, IN, 46556, USA"},{"name":"Mike and Josie Harper Cancer Research Institute, University of Notre Dame, South Bend, IN, 46617, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA"},{"name":"Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0910-3666","authenticated-orcid":false,"given":"Siyuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA"},{"name":"Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026051205050970000_2026.05.08.722799v1.1","doi-asserted-by":"crossref","unstructured":"Valls, P.O. & Esposito, A . Signalling dynamics, cell decisions, and homeostatic control in health and disease. Current Opinion in Cell Biology 75, 102066 (2022).","DOI":"10.1016\/j.ceb.2022.01.011"},{"key":"2026051205050970000_2026.05.08.722799v1.2","doi-asserted-by":"publisher","DOI":"10.1038\/nri3605"},{"key":"2026051205050970000_2026.05.08.722799v1.3","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-022-00682-8"},{"key":"2026051205050970000_2026.05.08.722799v1.4","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1038\/s41574-019-0298-z","article-title":"Integrated pathways that control stress and energy homeostasis","volume":"16","year":"2020","journal-title":"Nat Rev Endocrinol"},{"key":"2026051205050970000_2026.05.08.722799v1.5","doi-asserted-by":"crossref","unstructured":"Chiolo, I. , Altmeyer, M. , Legube, G. & Mekhail, K . Nuclear and genome dynamics underlying DNA double-strand break repair. Nat Rev Mol Cell Biol (2025).","DOI":"10.1038\/s41580-025-00828-1"},{"key":"2026051205050970000_2026.05.08.722799v1.6","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-021-00335-z"},{"key":"2026051205050970000_2026.05.08.722799v1.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2021.12.026"},{"key":"2026051205050970000_2026.05.08.722799v1.8","doi-asserted-by":"crossref","first-page":"2323","DOI":"10.1038\/s41588-025-02284-1","article-title":"Comprehensive transcription factor perturbations recapitulate fibroblast transcriptional states","volume":"57","year":"2025","journal-title":"Nat Genet"},{"key":"2026051205050970000_2026.05.08.722799v1.9","doi-asserted-by":"crossref","unstructured":"Magnusson, J.P. et al. PreciCE: Precision engineering of cell fates via data-driven multi-gene control of transcriptional networks. bioRxiv, 2024.2011.2004.621938 (2024).","DOI":"10.1101\/2024.11.04.621938"},{"key":"2026051205050970000_2026.05.08.722799v1.10","doi-asserted-by":"crossref","first-page":"1760","DOI":"10.1016\/j.stem.2024.10.007","article-title":"CRISPRi\/a screens in human iPSC-cardiomyocytes identify glycolytic activation as a druggable target for doxorubicin-induced cardiotoxicity","volume":"31","year":"2024","journal-title":"Cell Stem Cell"},{"key":"2026051205050970000_2026.05.08.722799v1.11","doi-asserted-by":"crossref","unstructured":"Schmidt, R. et al. CRISPR activation and interference screens decode stimulation responses in primary human T cells. Science 375, eabj4008 (2022).","DOI":"10.1126\/science.abj4008"},{"key":"2026051205050970000_2026.05.08.722799v1.12","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1038\/s41586-025-09489-8","article-title":"In vivo CRISPR screens identify modifiers of CAR T cell function in myeloma","volume":"646","year":"2025","journal-title":"Nature"},{"key":"2026051205050970000_2026.05.08.722799v1.13","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1038\/s41573-024-01100-5","article-title":"Novel strategies to manage CAR-T cell toxicity","volume":"24","year":"2025","journal-title":"Nat Rev Drug Discov"},{"key":"2026051205050970000_2026.05.08.722799v1.14","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-019-0152-0"},{"key":"2026051205050970000_2026.05.08.722799v1.15","doi-asserted-by":"crossref","unstructured":"Roidos, P. et al. A scalable CRISPR\/Cas9-based fluorescent reporter assay to study DNA double-strand break repair choice. Nat Commun 11, 4077 (2020).","DOI":"10.1038\/s41467-020-17962-3"},{"key":"2026051205050970000_2026.05.08.722799v1.16","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.09.029"},{"key":"2026051205050970000_2026.05.08.722799v1.17","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1016\/j.molcel.2026.01.025","article-title":"Large-scale mapping of environmental-genetic interactions illustrates the dynamic nature of cell-cycle and DNA repair regulation","volume":"86","year":"2026","journal-title":"Molecular Cell"},{"key":"2026051205050970000_2026.05.08.722799v1.18","doi-asserted-by":"crossref","unstructured":"Burrell, W.H. et al. Rational design of synthetic proteins using a genome-scale CRISPR screen. bioRxiv, 2026.2002.2019.706875 (2026).","DOI":"10.64898\/2026.02.19.706875"},{"key":"2026051205050970000_2026.05.08.722799v1.19","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-025-08815-4"},{"key":"2026051205050970000_2026.05.08.722799v1.20","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1038\/s41580-022-00571-x","article-title":"Revolutionizing DNA repair research and cancer therapy with CRISPR\u2013Cas screens","volume":"24","year":"2023","journal-title":"Nature Reviews Molecular Cell Biology"},{"key":"2026051205050970000_2026.05.08.722799v1.21","doi-asserted-by":"publisher","DOI":"10.1016\/J.CELL.2021.10.002"},{"key":"2026051205050970000_2026.05.08.722799v1.22","doi-asserted-by":"crossref","unstructured":"Bowden, A.R. et al. Parallel CRISPR-Cas9 screens clarify impacts of p53 on screen performance. Elife 9 (2020).","DOI":"10.7554\/eLife.55325"},{"key":"2026051205050970000_2026.05.08.722799v1.23","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2023.07.004"},{"key":"2026051205050970000_2026.05.08.722799v1.24","doi-asserted-by":"crossref","unstructured":"Hartman, A. et al. A unified genetic perturbation language for human cellular programming. bioRxiv, 2025.2011.2020.689421 (2025).","DOI":"10.1101\/2025.11.20.689421"},{"key":"2026051205050970000_2026.05.08.722799v1.25","doi-asserted-by":"crossref","unstructured":"Pacalin, N.M. et al. Bidirectional epigenetic editing reveals hierarchies in gene regulation. Nature Biotechnology (2024).","DOI":"10.1038\/s41587-024-02213-3"},{"key":"2026051205050970000_2026.05.08.722799v1.26","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-023-01554-0"},{"key":"2026051205050970000_2026.05.08.722799v1.27","doi-asserted-by":"crossref","unstructured":"Shaw, W.M. et al. Inducible expression of large gRNA arrays for multiplexed CRISPRai applications. Nature Communications 13, 4984 (2022).","DOI":"10.1038\/s41467-022-32603-7"},{"key":"2026051205050970000_2026.05.08.722799v1.28","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-022-01131-4"},{"key":"2026051205050970000_2026.05.08.722799v1.29","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-022-01131-x"},{"key":"2026051205050970000_2026.05.08.722799v1.30","doi-asserted-by":"crossref","first-page":"1998","DOI":"10.1021\/acssynbio.8b00527","article-title":"Systematic Evaluation of CRISPRa and CRISPRi Modalities Enables Development of a Multiplexed, Orthogonal Gene Activation and Repression System","volume":"8","year":"2019","journal-title":"ACS Synthetic Biology"},{"key":"2026051205050970000_2026.05.08.722799v1.31","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.4062"},{"key":"2026051205050970000_2026.05.08.722799v1.32","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.3390"},{"key":"2026051205050970000_2026.05.08.722799v1.33","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4042"},{"key":"2026051205050970000_2026.05.08.722799v1.34","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz267"},{"key":"2026051205050970000_2026.05.08.722799v1.35","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2022.05.013"},{"key":"2026051205050970000_2026.05.08.722799v1.36","doi-asserted-by":"publisher","DOI":"10.1126\/science.aax4438"},{"key":"2026051205050970000_2026.05.08.722799v1.37","doi-asserted-by":"publisher","DOI":"10.1038\/nature14136"},{"key":"2026051205050970000_2026.05.08.722799v1.38","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2024.01.042"},{"key":"2026051205050970000_2026.05.08.722799v1.39","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.02.033"},{"key":"2026051205050970000_2026.05.08.722799v1.40","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.09.001"},{"key":"2026051205050970000_2026.05.08.722799v1.41","doi-asserted-by":"publisher","DOI":"10.1002\/CPZ1.846"},{"key":"2026051205050970000_2026.05.08.722799v1.42","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3312"},{"key":"2026051205050970000_2026.05.08.722799v1.43","doi-asserted-by":"crossref","unstructured":"Zhang, B. et al. Two HEPN domains dictate CRISPR RNA maturation and target cleavage in Cas13d. Nature Communications 10, 2544 (2019).","DOI":"10.1038\/s41467-019-10507-3"},{"key":"2026051205050970000_2026.05.08.722799v1.44","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.02.001"},{"key":"2026051205050970000_2026.05.08.722799v1.45","doi-asserted-by":"publisher","DOI":"10.1038\/nature19802"},{"key":"2026051205050970000_2026.05.08.722799v1.46","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.12.031"},{"key":"2026051205050970000_2026.05.08.722799v1.47","doi-asserted-by":"crossref","unstructured":"Chang, C. , Ma, G. , Cheung, E. & Hutchins, A.P . A programmable system to methylate and demethylate N6-Methyladenosine (m6A) on specific RNA transcripts in mammalian cells. Journal of Biological Chemistry (2022).","DOI":"10.1016\/j.jbc.2022.102525"},{"key":"2026051205050970000_2026.05.08.722799v1.48","doi-asserted-by":"publisher","DOI":"10.1038\/S41586-024-07487-W"},{"key":"2026051205050970000_2026.05.08.722799v1.49","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.1016\/j.gpb.2022.12.003","article-title":"Superior Fidelity and Distinct Editing Outcomes of SaCas9 Compared with SpCas9 in Genome Editing","volume":"21","year":"2023","journal-title":"Genomics Proteomics Bioinformatics"},{"key":"2026051205050970000_2026.05.08.722799v1.50","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-024-02320-1"},{"key":"2026051205050970000_2026.05.08.722799v1.51","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4104"},{"key":"2026051205050970000_2026.05.08.722799v1.52","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkg331"},{"key":"2026051205050970000_2026.05.08.722799v1.53","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2204259119"},{"key":"2026051205050970000_2026.05.08.722799v1.54","doi-asserted-by":"crossref","unstructured":"Leuzzi, G. et al. SMARCAL1 is a dual regulator of innate immune signaling and PD-L1 expression that promotes tumor immune evasion. Cell (2024).","DOI":"10.1016\/j.cell.2024.01.008"},{"key":"2026051205050970000_2026.05.08.722799v1.55","doi-asserted-by":"crossref","unstructured":"Deshpande, R.A. et al. Genome-wide analysis of DNA-PK-bound MRN cleavage products supports a sequential model of DSB repair pathway choice. Nat Commun 14, 5759 (2023).","DOI":"10.1038\/s41467-023-41544-8"},{"key":"2026051205050970000_2026.05.08.722799v1.56","doi-asserted-by":"crossref","unstructured":"Reint, G. et al. Rapid genome editing by CRISPR-Cas9-POLD3 fusion. Elife 10 (2021).","DOI":"10.7554\/eLife.75415"},{"key":"2026051205050970000_2026.05.08.722799v1.57","doi-asserted-by":"crossref","unstructured":"Su, D. et al. CRISPR\/CAS9-based DNA damage response screens reveal gene-drug interactions. DNA Repair 87, 102803 (2020).","DOI":"10.1016\/j.dnarep.2020.102803"},{"key":"2026051205050970000_2026.05.08.722799v1.58","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz487"},{"key":"2026051205050970000_2026.05.08.722799v1.59","doi-asserted-by":"crossref","unstructured":"Simpson, D. , Ling, J. , Jing, Y. & Adamson, B. Mapping the Genetic Interaction Network of PARP inhibitor Response. bioRxiv, 2023.2008.2019.553986 (2023).","DOI":"10.1101\/2023.08.19.553986"},{"key":"2026051205050970000_2026.05.08.722799v1.60","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-021-00938-z"},{"key":"2026051205050970000_2026.05.08.722799v1.61","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.09.018"},{"key":"2026051205050970000_2026.05.08.722799v1.62","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2426"},{"key":"2026051205050970000_2026.05.08.722799v1.63","doi-asserted-by":"crossref","unstructured":"Cullot, G. et al. Genome editing with the HDR-enhancing DNA-PKcs inhibitor AZD7648 causes large-scale genomic alterations. Nat Biotechnol (2024).","DOI":"10.1038\/s41587-024-02488-6"},{"key":"2026051205050970000_2026.05.08.722799v1.64","doi-asserted-by":"crossref","unstructured":"Rees, H.A. , Yeh, W.H. & Liu, D.R . Development of hRad51-Cas9 nickase fusions that mediate HDR without double-stranded breaks. Nat Commun 10, 2212 (2019).","DOI":"10.1038\/s41467-019-09983-4"},{"key":"2026051205050970000_2026.05.08.722799v1.65","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkad255"},{"key":"2026051205050970000_2026.05.08.722799v1.66","doi-asserted-by":"crossref","unstructured":"Charpentier, M. et al. CtIP fusion to Cas9 enhances transgene integration by homology-dependent repair. Nat Commun 9, 1133 (2018).","DOI":"10.1038\/s41467-018-03475-7"},{"key":"2026051205050970000_2026.05.08.722799v1.67","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.4021"},{"key":"2026051205050970000_2026.05.08.722799v1.68","doi-asserted-by":"publisher","DOI":"10.1038\/nature24023"},{"key":"2026051205050970000_2026.05.08.722799v1.69","doi-asserted-by":"crossref","unstructured":"Jayavaradhan, R. et al. CRISPR-Cas9 fusion to dominant-negative 53BP1 enhances HDR and inhibits NHEJ specifically at Cas9 target sites. Nat Commun 10, 2866 (2019).","DOI":"10.1038\/s41467-019-10735-7"},{"key":"2026051205050970000_2026.05.08.722799v1.70","doi-asserted-by":"crossref","unstructured":"Tran, N.T. et al. Enhancement of Precise Gene Editing by the Association of Cas9 With Homologous Recombination Factors. Front Genet 10, 365 (2019).","DOI":"10.3389\/fgene.2019.00365"},{"key":"2026051205050970000_2026.05.08.722799v1.71","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1038\/s41551-017-0145-2","article-title":"Ectopic expression of RAD52 and dn53BP1 improves homology-directed repair during CRISPR-Cas9 genome editing","volume":"1","year":"2017","journal-title":"Nat Biomed Eng"},{"key":"2026051205050970000_2026.05.08.722799v1.72","doi-asserted-by":"crossref","unstructured":"Savic, N. et al. Covalent linkage of the DNA repair template to the CRISPR-Cas9 nuclease enhances homology-directed repair. Elife 7 (2018).","DOI":"10.7554\/eLife.33761"},{"key":"2026051205050970000_2026.05.08.722799v1.73","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv993"},{"key":"2026051205050970000_2026.05.08.722799v1.74","doi-asserted-by":"crossref","unstructured":"Wang, J.Y. & Doudna, J.A . CRISPR technology: A decade of genome editing is only the beginning. Science 379, eadd8643 (2023).","DOI":"10.1126\/science.add8643"},{"key":"2026051205050970000_2026.05.08.722799v1.75","doi-asserted-by":"publisher","DOI":"10.1021\/acschembio.7b00760"},{"key":"2026051205050970000_2026.05.08.722799v1.76","doi-asserted-by":"crossref","unstructured":"Falbo, L. & Costanzo, V . Replicative gaps in DNA damage tolerance, genome instability, and cancer therapy. Mol Cell (2026).","DOI":"10.1016\/j.molcel.2026.02.018"},{"key":"2026051205050970000_2026.05.08.722799v1.77","doi-asserted-by":"crossref","unstructured":"Bantele, S. et al. Repair of DNA double-strand breaks leaves heritable impairment to genome function. Science 390, eadk6662 (2025).","DOI":"10.1126\/science.adk6662"},{"key":"2026051205050970000_2026.05.08.722799v1.78","doi-asserted-by":"crossref","unstructured":"van de Kooij, B. , Kruswick, A. , van Attikum, H. & Yaffe, M.B . Multi-pathway DNA-repair reporters reveal competition between end-joining, single-strand annealing and homologous recombination at Cas9-induced DNA double-strand breaks. Nat Commun 13, 5295 (2022).","DOI":"10.1038\/s41467-022-32743-w"},{"key":"2026051205050970000_2026.05.08.722799v1.79","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03458-7"},{"key":"2026051205050970000_2026.05.08.722799v1.80","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-019-03365-1"},{"key":"2026051205050970000_2026.05.08.722799v1.81","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-genet-110410-132435"},{"key":"2026051205050970000_2026.05.08.722799v1.82","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.09.029"},{"key":"2026051205050970000_2026.05.08.722799v1.83","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2017.05.015"},{"key":"2026051205050970000_2026.05.08.722799v1.84","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2010.09.019"},{"key":"2026051205050970000_2026.05.08.722799v1.85","doi-asserted-by":"crossref","first-page":"e334","DOI":"10.1038\/mtna.2016.48","article-title":"GFP to BFP Conversion: A Versatile Assay for the Quantification of CRISPR\/Cas9-mediated Genome Editing","volume":"5","year":"2016","journal-title":"Molecular Therapy - Nucleic Acids"},{"key":"2026051205050970000_2026.05.08.722799v1.86","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2022.12.003"},{"key":"2026051205050970000_2026.05.08.722799v1.87","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2016.10.010"},{"key":"2026051205050970000_2026.05.08.722799v1.88","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2009.12.002"},{"key":"2026051205050970000_2026.05.08.722799v1.89","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-020-00519-1"},{"key":"2026051205050970000_2026.05.08.722799v1.90","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1038\/nmeth.4104","article-title":"In vivo high-throughput profiling of CRISPR\u2013Cpf1 activity","volume":"14","year":"2017","journal-title":"Nature Methods"},{"key":"2026051205050970000_2026.05.08.722799v1.91","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-019-0032-3"},{"key":"2026051205050970000_2026.05.08.722799v1.92","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1038\/nmeth.4177","article-title":"Pooled CRISPR screening with single-cell transcriptome readout","volume":"14","year":"2017","journal-title":"Nature Methods"},{"key":"2026051205050970000_2026.05.08.722799v1.93","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.11.038"},{"key":"2026051205050970000_2026.05.08.722799v1.94","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.11.048"},{"key":"2026051205050970000_2026.05.08.722799v1.95","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-020-0470-y"},{"key":"2026051205050970000_2026.05.08.722799v1.96","doi-asserted-by":"crossref","unstructured":"Jin, X. et al. In vivo Perturb-Seq reveals neuronal and glial abnormalities associated with autism risk genes. Science 370, eaaz6063 (2020).","DOI":"10.1126\/science.aaz6063"},{"key":"2026051205050970000_2026.05.08.722799v1.97","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btac076"},{"key":"2026051205050970000_2026.05.08.722799v1.98","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0506580102"},{"key":"2026051205050970000_2026.05.08.722799v1.99","doi-asserted-by":"publisher","DOI":"10.1016\/J.CELS.2015.12.004"},{"key":"2026051205050970000_2026.05.08.722799v1.100","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3719"},{"key":"2026051205050970000_2026.05.08.722799v1.101","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4463"},{"key":"2026051205050970000_2026.05.08.722799v1.102","doi-asserted-by":"publisher","DOI":"10.1038\/nature21405"},{"key":"2026051205050970000_2026.05.08.722799v1.103","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0326-5"},{"key":"2026051205050970000_2026.05.08.722799v1.104","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.3481"},{"key":"2026051205050970000_2026.05.08.722799v1.105","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.3737"},{"key":"2026051205050970000_2026.05.08.722799v1.106","doi-asserted-by":"crossref","unstructured":"Villiger, L. et al. CRISPR technologies for genome, epigenome and transcriptome editing. Nature Reviews Molecular Cell Biology (2024).","DOI":"10.1038\/s41580-023-00697-6"},{"key":"2026051205050970000_2026.05.08.722799v1.107","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05531-1"},{"key":"2026051205050970000_2026.05.08.722799v1.108","doi-asserted-by":"crossref","first-page":"1821","DOI":"10.1038\/s41587-024-02504-9","article-title":"Efficient non-viral immune cell engineering using circular single-stranded DNA-mediated genomic integration","volume":"43","year":"2025","journal-title":"Nature Biotechnology"},{"key":"2026051205050970000_2026.05.08.722799v1.109","doi-asserted-by":"crossref","unstructured":"Roth, T.L. et al. Non-viral intron knock-ins for targeted gene integration into human T cells and for T-cell selection. Nature Biomedical Engineering (2025).","DOI":"10.1038\/s41551-025-01372-1"},{"key":"2026051205050970000_2026.05.08.722799v1.110","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-023-01779-8"},{"key":"2026051205050970000_2026.05.08.722799v1.111","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-022-01418-8"},{"key":"2026051205050970000_2026.05.08.722799v1.112","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1038\/s41586-026-10235-x","article-title":"In vivo site-specific engineering to reprogram T cells","volume":"652","year":"2026","journal-title":"Nature"},{"key":"2026051205050970000_2026.05.08.722799v1.113","first-page":"149","article-title":"Enhancement of the viability of T cells electroporated with DNA via osmotic dampening of the DNA-sensing cGAS-STING pathway","volume":"8","year":"2024","journal-title":"Nat Biomed Eng"},{"key":"2026051205050970000_2026.05.08.722799v1.114","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.02.029"},{"key":"2026051205050970000_2026.05.08.722799v1.115","doi-asserted-by":"publisher","DOI":"10.1016\/J.CELL.2023.08.041"},{"key":"2026051205050970000_2026.05.08.722799v1.116","unstructured":"Stadtmauer, E.A. et al. CRISPR-engineered T cells in patients with refractory cancer. Science 367, eaba7365 (2020)."},{"key":"2026051205050970000_2026.05.08.722799v1.117","doi-asserted-by":"crossref","unstructured":"Ray, U. , Vartak, S.V. & Raghavan, S.C . NHEJ inhibitor SCR7 and its different forms: Promising CRISPR tools for genome engineering. Gene 763, 144997 (2020).","DOI":"10.1016\/j.gene.2020.144997"},{"key":"2026051205050970000_2026.05.08.722799v1.118","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.11.054"},{"key":"2026051205050970000_2026.05.08.722799v1.119","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1089\/crispr.2023.0036","article-title":"Enhancing Precision and Efficiency of Cas9-Mediated Knockin Through Combinatorial Fusions of DNA Repair Proteins","volume":"6","year":"2023","journal-title":"The CRISPR Journal"},{"key":"2026051205050970000_2026.05.08.722799v1.120","first-page":"177","article-title":"Intrinsic targeting of host RNA by Cas13 constrains its utility","volume":"8","year":"2024","journal-title":"Nature Biomedical Engineering"},{"key":"2026051205050970000_2026.05.08.722799v1.121","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1038\/s41587-025-02558-3","article-title":"Precise RNA targeting with CRISPR\u2013Cas13d","volume":"44","year":"2026","journal-title":"Nature Biotechnology"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.05.08.722799","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T12:05:56Z","timestamp":1778587556000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.05.08.722799"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,8]]},"references-count":121,"URL":"https:\/\/doi.org\/10.64898\/2026.05.08.722799","relation":{},"subject":[],"published":{"date-parts":[[2026,5,8]]},"subtype":"preprint"}}