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Welfare Act and Regulations, the Guide for the Care and Use of Laboratory Animals and the University of Washington's Institutional Animal Care and Use Committee (IACUC) policies. The studies were approved by the IACUC of the University of Washington (Protocol No. 3108-01). Authors contributions: A.L. and C.L. provided the conceptual framework for the study. A.L., C.L., A.G. and E.N. designed the experiments. C.L., A.G., G.A.N., K.E., E.N., P.K., S.G., H.W., A.K.A., L.H., T.K. and H.W. performed the experiments. D.R.L provided critical comments on the manuscript. A.L. wrote the manuscript. Acknowledgements The study was supported by NIH grants R01HL128288 (A.L.), R01HL130040 (A.L.), R01HL141781 A.L.), U01 AI142756 (D.R.L.), RM1 HG009490 (D.R.L.), R35 GM118062 (D.R.L.), by a grant from Ensoma Bio (A.L., HP.K.), and by grants from the Bill and Melinda Gates Foundation: (A.L.) and (D.R.L.), and the HHMI (D.R.L.). G.A.N. was supported by a Helen Hay Whitney Postdoctoral Fellowship and K99 award HL163805. Under the grant conditions of the BMGF, a Creative Commons Attribution 4.0 Generic License has already been assigned to the Author Accepted Manuscript version that might arise from this submission. References 1. Li C, and Lieber A. Adenovirus vectors in hematopoietic stem cell genome editing. FEBS Lett. 2019;593(24):3623-48. 2. Richter M, Saydaminova K, Yumul R, Krishnan R, Liu J, Nagy EE, et al. In vivo transduction of primitive mobilized hematopoietic stem cells after intravenous injection of integrating adenovirus vectors. Blood. 2016;128(18):2206-17. 3. Wang H, Germond A, Li C, Gil S, Kim J, Kiem HP, et al. In vivo HSC transduction in rhesus macaques with an HDAd5/3+ vector targeting desmoglein 2 and transiently overexpressing cxcr4. Blood Adv. 2022;6(15):4360-72. 4. Yu VW, and Scadden DT. Hematopoietic Stem Cell and Its Bone Marrow Niche. Curr Top Dev Biol. 2016;118:21-44.