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Yet, an outstanding bottleneck for its optimization and use concerns the difficulty in delivering large prime editing complexes into cells. Here, we demonstrate that packaging prime editing constructs in adenoviral capsids overcomes this constrain resulting in robust genome editing in both transformed and non-transformed human cells with up to 90% efficiencies. Using this cell cycle-independent delivery platform, we found a direct correlation between prime editing activity and cellular replication and disclose that the proportions between accurate prime editing events and unwanted byproducts can be influenced by the target-cell context. Hence, adenovector particles permit the efficacious delivery and testing of prime editing reagents in human cells independently of their transformation and replication statuses. The herein integrated gene delivery and gene editing technologies are expected to aid investigating the potential and limitations of prime editing in numerous experimental settings and, eventually, in ex vivo or in vivo therapeutic contexts.<\/jats:p>","DOI":"10.1093\/nar\/gkab938","type":"journal-article","created":{"date-parts":[[2021,9,30]],"date-time":"2021-09-30T12:00:32Z","timestamp":1633003232000},"page":"11986-12001","source":"Crossref","is-referenced-by-count":45,"title":["Broadening the reach and investigating the potential of prime editors through fully viral gene-deleted adenoviral vector delivery"],"prefix":"10.1093","volume":"49","author":[{"given":"Qian","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Cell and Chemical Biology, Leiden University Medical Center, Einthovenweg 20, 2333 ZC\u00a0Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Cell and Chemical Biology, Leiden University Medical Center, Einthovenweg 20, 2333 ZC\u00a0Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josephine M","family":"Janssen","sequence":"additional","affiliation":[{"name":"Department of Cell and Chemical Biology, Leiden University Medical Center, Einthovenweg 20, 2333 ZC\u00a0Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Tasca","sequence":"additional","affiliation":[{"name":"Department of Cell and Chemical Biology, Leiden University Medical Center, Einthovenweg 20, 2333 ZC\u00a0Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1781-5508","authenticated-orcid":false,"given":"Hailiang","family":"Mei","sequence":"additional","affiliation":[{"name":"Department of Biomedical Data Sciences, Sequencing Analysis Support Core, Leiden University Medical Center, Einthovenweg 20, 2333 ZC\u00a0Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8111-1073","authenticated-orcid":false,"given":"Manuel A F V","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"Department of Cell and Chemical Biology, Leiden University Medical Center, Einthovenweg 20, 2333 ZC\u00a0Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,10,20]]},"reference":[{"key":"2021111805161659700_B1","doi-asserted-by":"crossref","first-page":"E2579","DOI":"10.1073\/pnas.1208507109","article-title":"Cas9-crRNA ribonucleoprotein complex mediates specific DNA cleavage for adaptive immunity in bacteria","volume":"109","author":"Gasiunas","year":"2012","journal-title":"Proc. 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