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HUH site-specific recombinases for targeted modification of the human genome

Paper ID Volume ID Publish Year Pages File Format Full-Text
37076 45308 2013 8 PDF Available
Title
HUH site-specific recombinases for targeted modification of the human genome
Abstract

•SSRs offer attractive features for targeted genome modification.•HUH SSRs can integrate ssDNA with the aid of host replication machinery.•AAV Rep and R388-TrwC can be delivered in vivo.•Rep-mediated integration into AAVS1 does not have adverse effects.

Site-specific recombinases (SSRs) have been crucial in the development of mammalian transgenesis. For gene therapy purposes, this approach remains challenging, because, for example, SSR delivery is largely unresolved and SSR DNA substrates must pre-exist in target cells. In this review, we discuss the potential of His-hydrophobic-His (HUH) recombinases to overcome some of the limitations of conventional SSRs. Members of the HUH protein family cleave single-stranded (ss)DNA, but can mediate site-specific integration with the aid of the host replication machinery. Adeno-associated virus (AAV) Rep remains the only known example to support site-specific integration in human cells, and AAV is an excellent gene delivery vector that can be targeted to specific cells and organelles. Bacterial protein TrwC catalyzes integration into human sequences and can be delivered to human cells covalently linked to DNA, offering attractive new features for targeted genome modification.

Keywords
genomic engineering; site-specific recombination; gene therapy; HUH family; AAV Rep; R388 TrwC
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HUH site-specific recombinases for targeted modification of the human genome
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Publisher
Database: Elsevier - ScienceDirect
Journal: - Volume 31, Issue 5, May 2013, Pages 305–312
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us