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An advantage of this approach is that corrected iPSCs that are free of off-target modifications can be identified before differentiating the cells into hematopoietic progenitors for transplantation. In order for this approach to be practical, iPSC generation must be rapid and efficient. Therefore, we developed a novel helper-dependent adenovirus\/Epstein-Barr virus (HDAd\/EBV) hybrid reprogramming vector, rCLAE-R6, that delivers six reprogramming factors episomally. HDAd\/EBV transduction of keratinocytes from SCD patients resulted in footprint-free iPSCs with high efficiency. Subsequently, the sickle mutation was corrected by delivering CRISPR\/Cas9 with adenovirus followed by nucleoporation with a 70\u2009nt single-stranded oligodeoxynucleotide (ssODN) correction template. Correction efficiencies of up to 67.9% (\u03b2\n                    <jats:sup>A<\/jats:sup>\n                    \/[\u03b2\n                    <jats:sup>S<\/jats:sup>\n                    +\u03b2\n                    <jats:sup>A<\/jats:sup>\n                    ]) were obtained. Whole-genome sequencing (WGS) of corrected iPSC lines demonstrated no CRISPR\/Cas modifications in 1467 potential off-target sites and no modifications in tumor suppressor genes or other genes associated with pathologies. These results demonstrate that adenoviral delivery of reprogramming factors and CRISPR\/Cas provides a rapid and efficient method of deriving gene-corrected, patient-specific iPSCs for therapeutic applications.\n                  <\/jats:p>","DOI":"10.1038\/srep30422","type":"journal-article","created":{"date-parts":[[2016,7,27]],"date-time":"2016-07-27T04:52:57Z","timestamp":1469595177000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Novel HDAd\/EBV Reprogramming Vector and Highly Efficient Ad\/CRISPR-Cas Sickle Cell Disease Gene Correction"],"prefix":"10.1038","volume":"6","author":[{"given":"Chao","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiao-Wang","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Chen","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dewang","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin M.","family":"Pawlik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alireza","family":"Khodadadi-Jamayran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik","family":"Westin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederick D.","family":"Goldman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim M.","family":"Townes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,7,27]]},"reference":[{"key":"BFsrep30422_CR1","doi-asserted-by":"publisher","first-page":"792","DOI":"10.1038\/178792a0","volume":"178","author":"VM Ingram","year":"1956","unstructured":"Ingram, V. 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