Details:

Alternative Title:
Cell Rep
Publisher's site:
http://dx.doi.org/10.1016/j.celrep.2015.07.019
Personal Author:
Zinn, Eric ; Pacouret, Simon ; Khaychuk, Vadim ; Turunen, Heikki T. ; Carvalho, Livia S. ; ... More +
Zinn, Eric ; Pacouret, Simon ; Khaychuk, Vadim ; Turunen, Heikki T. ; Carvalho, Livia S. ; Andres-Mateos, Eva ; Shah, Samiksha ; Shelke, Rajani ; Maurer, Anna C. ; Plovie, Eva ; Xiao, Ru ; Vandenberghe, Luk H. Less -
Description:
Adeno-associated virus (AAV) vectors have emerged as a gene-delivery platform with demonstrated safety and efficacy in a handful of clinical trials for monogenic disorders. However, limitations of the current generation vectors often prevent broader application of AAV gene therapy. Efforts to engineer AAV vectors have been hampered by a limited understanding of the structure-function relationship of the complex multimeric icosahedral architecture of the particle. To develop additional reagents pertinent to further our insight into AAVs, we inferred evolutionary intermediates of the viral capsid using ancestral sequence reconstruction. In-silico-derived sequences were synthesized de novo and characterized for biological properties relevant to clinical applications. This effort led to the generation of nine functional putative ancestral AAVs and the identification of Anc80, the predicted ancestor of the widely studied AAV serotypes 1, 2, 8, and 9, as a highly potent in vivo gene therapy vector for targeting liver, muscle, and retina.
Subject:
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AAV Adeno-associated Virus Ancestral Reconstruction Article Capsid T-cell Dependovirus Gene Therapy Genetic Therapy Genetic Vectors Gene Transfer Gene Transfer Techniques Molecular Sequence Data Neutralizing Antibody Pre-existing Immunity Synthetic Biology Vaccine Vector Virus
Source:
Cell Rep. 12(6):1056-1068.
Pubmed ID:
26235624
Pubmed Central ID:
PMC4536165
Document Type:
Journal Article
Funding:
5DP1EY023177-03/DP/NCCDPHP CDC HHS/United States ; DP1 EY023177/EY/NEI NIH HHS/United States ; DP1 OD008267/OD/NIH HHS/United States
5DP1EY023177-03/DP/NCCDPHP CDC HHS/United States ; DP1 EY023177/EY/NEI NIH HHS/United States ; DP1 OD008267/OD/NIH HHS/United States Less -
Collection(s):
CDC Public Access
Main Document Checksum:
[+]
urn:sha256:6bd8345ff25df1affcd69bb4cea2b823da7ab4655623c06da33bb2486e8d9836
Download URL:
https://stacks.cdc.gov/view/cdc/35070/cdc_35070_DS1.pdf
File Type:

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