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A systematic capsid evolution approach performed in vivo for the design of AAV vectors with tailored properties and tropism
Adeno-associated virus (AAV) capsid modification enables the generation of recombinant vectors with tailored properties and tropism. Most approaches to date depend on random screening, enrichment, and serendipity. The approach explored here, called BRAVE (barcoded rational AAV vector evolution), ena...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
National Academy of Sciences
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6936499/ https://www.ncbi.nlm.nih.gov/pubmed/31818949 http://dx.doi.org/10.1073/pnas.1910061116 |
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author | Davidsson, Marcus Wang, Gang Aldrin-Kirk, Patrick Cardoso, Tiago Nolbrant, Sara Hartnor, Morgan Mudannayake, Janitha Parmar, Malin Björklund, Tomas |
author_facet | Davidsson, Marcus Wang, Gang Aldrin-Kirk, Patrick Cardoso, Tiago Nolbrant, Sara Hartnor, Morgan Mudannayake, Janitha Parmar, Malin Björklund, Tomas |
author_sort | Davidsson, Marcus |
collection | PubMed |
description | Adeno-associated virus (AAV) capsid modification enables the generation of recombinant vectors with tailored properties and tropism. Most approaches to date depend on random screening, enrichment, and serendipity. The approach explored here, called BRAVE (barcoded rational AAV vector evolution), enables efficient selection of engineered capsid structures on a large scale using only a single screening round in vivo. The approach stands in contrast to previous methods that require multiple generations of enrichment. With the BRAVE approach, each virus particle displays a peptide, derived from a protein, of known function on the AAV capsid surface, and a unique molecular barcode in the packaged genome. The sequencing of RNA-expressed barcodes from a single-generation in vivo screen allows the mapping of putative binding sequences from hundreds of proteins simultaneously. Using the BRAVE approach and hidden Markov model-based clustering, we present 25 synthetic capsid variants with refined properties, such as retrograde axonal transport in specific subtypes of neurons, as shown for both rodent and human dopaminergic neurons. |
format | Online Article Text |
id | pubmed-6936499 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | National Academy of Sciences |
record_format | MEDLINE/PubMed |
spelling | pubmed-69364992019-12-31 A systematic capsid evolution approach performed in vivo for the design of AAV vectors with tailored properties and tropism Davidsson, Marcus Wang, Gang Aldrin-Kirk, Patrick Cardoso, Tiago Nolbrant, Sara Hartnor, Morgan Mudannayake, Janitha Parmar, Malin Björklund, Tomas Proc Natl Acad Sci U S A PNAS Plus Adeno-associated virus (AAV) capsid modification enables the generation of recombinant vectors with tailored properties and tropism. Most approaches to date depend on random screening, enrichment, and serendipity. The approach explored here, called BRAVE (barcoded rational AAV vector evolution), enables efficient selection of engineered capsid structures on a large scale using only a single screening round in vivo. The approach stands in contrast to previous methods that require multiple generations of enrichment. With the BRAVE approach, each virus particle displays a peptide, derived from a protein, of known function on the AAV capsid surface, and a unique molecular barcode in the packaged genome. The sequencing of RNA-expressed barcodes from a single-generation in vivo screen allows the mapping of putative binding sequences from hundreds of proteins simultaneously. Using the BRAVE approach and hidden Markov model-based clustering, we present 25 synthetic capsid variants with refined properties, such as retrograde axonal transport in specific subtypes of neurons, as shown for both rodent and human dopaminergic neurons. National Academy of Sciences 2019-12-26 2019-12-09 /pmc/articles/PMC6936499/ /pubmed/31818949 http://dx.doi.org/10.1073/pnas.1910061116 Text en Copyright © 2019 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/ https://creativecommons.org/licenses/by-nc-nd/4.0/This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) . |
spellingShingle | PNAS Plus Davidsson, Marcus Wang, Gang Aldrin-Kirk, Patrick Cardoso, Tiago Nolbrant, Sara Hartnor, Morgan Mudannayake, Janitha Parmar, Malin Björklund, Tomas A systematic capsid evolution approach performed in vivo for the design of AAV vectors with tailored properties and tropism |
title | A systematic capsid evolution approach performed in vivo for the design of AAV vectors with tailored properties and tropism |
title_full | A systematic capsid evolution approach performed in vivo for the design of AAV vectors with tailored properties and tropism |
title_fullStr | A systematic capsid evolution approach performed in vivo for the design of AAV vectors with tailored properties and tropism |
title_full_unstemmed | A systematic capsid evolution approach performed in vivo for the design of AAV vectors with tailored properties and tropism |
title_short | A systematic capsid evolution approach performed in vivo for the design of AAV vectors with tailored properties and tropism |
title_sort | systematic capsid evolution approach performed in vivo for the design of aav vectors with tailored properties and tropism |
topic | PNAS Plus |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6936499/ https://www.ncbi.nlm.nih.gov/pubmed/31818949 http://dx.doi.org/10.1073/pnas.1910061116 |
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