Sites in the AAV5 capsid tolerant to deletions and tandem duplications.

Archives of Biochemistry and Biophysics
Kaoru HidaMarc Ostermeier

Abstract

Gene therapy vectors based on adeno-associated virus (AAV) have shown much promise in clinical trials for the treatment of a variety of diseases. However, the ability to manipulate and engineer the viral surface for enhanced efficiency is necessary to overcome such barriers as pre-existing immunity and transduction of non-target cells that currently limit AAV applications. Although single amino acid changes and peptide insertions at select sites have been explored previously, the tolerance of AAV to small deletions and tandem duplications of sequence has not been globally addressed. Here, we have generated a large, diverse library of >10(5) members containing deletions and tandem duplications throughout the viral capsid of AAV5. Four unique mutants were identified that maintain the ability to form viral particles, with one showing improved transduction on both 293T and BEAS-2B cells. This approach may find potential use for the generation of novel variants with improved and altered properties or in the identification of sites that are tolerant to insertions of targeting ligands.

References

Jan 27, 2004·Journal of Molecular Biology·Gurkan Guntas, Marc Ostermeier
Nov 15, 2005·The Journal of Gene Medicine·Luca PeraboHildegard Büning

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Citations

Feb 10, 2012·Nucleic Acids Research·Manan M MehtaJonathan J Silberg
Jun 7, 2012·Protein Engineering, Design & Selection : PEDS·Yakov KipnisDan S Tawfik
Sep 10, 2014·Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology·Caitlin M GuentherJunghae Suh
May 15, 2013·Scientific Reports·Dwaipayan SenGiridhara R Jayandharan
Aug 9, 2013·Journal of Virology·Lakshmanan GovindasamyMavis Agbandje-McKenna
Jan 29, 2017·Nucleic Acids Research·Aleardo MorelliBurckhard Seelig
Jul 16, 2021·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Lorea AlejaldreDaniela Quaglia

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