
DNA Recombinases as Genome Editing Tools The Harvard community has made this article openly available. Please share how this access benefits you. Your story matters Citation Bessen, Jeffrey L. 2019. DNA Recombinases as Genome Editing Tools. Doctoral dissertation, Harvard University, Graduate School of Arts & Sciences. Citable link http://nrs.harvard.edu/urn-3:HUL.InstRepos:42029711 Terms of Use This article was downloaded from Harvard University’s DASH repository, and is made available under the terms and conditions applicable to Other Posted Material, as set forth at http:// nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of- use#LAA ! ! "#$!%&'()*+,-.&.!-.!/&,()&!01+2+,3!4((5.! ! ! ! ! "!#$%%&'()($*+!,'&%&+(&#! -.! /&00'&.!1)2'&+3&!4&%%&+! 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