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A systematic capsid evolution approach performed in vivo for the design of AAV vectors with tailored properties and tropism

Davidsson, Marcus LU ; Wang, Gang LU ; Aldrin-Kirk, Patrick LU ; Cardoso, Tiago LU ; Nolbrant, Sara LU ; Hartnor, Morgan ; Mudannayake, Janitha LU orcid ; Parmar, Malin LU orcid and Björklund, Tomas LU (2019) In Proceedings of the National Academy of Sciences of the United States of America 116(52). p.27053-27062
Abstract

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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Proceedings of the National Academy of Sciences of the United States of America
volume
116
issue
52
pages
10 pages
publisher
National Academy of Sciences
external identifiers
  • pmid:31818949
  • scopus:85077269512
ISSN
1091-6490
DOI
10.1073/pnas.1910061116
language
English
LU publication?
yes
additional info
Copyright © 2019 the Author(s). Published by PNAS.
id
7131509a-1d12-48d3-826c-1654f767344e
date added to LUP
2019-12-12 13:53:23
date last changed
2024-05-01 02:14:43
@article{7131509a-1d12-48d3-826c-1654f767344e,
  abstract     = {{<p>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.</p>}},
  author       = {{Davidsson, Marcus and Wang, Gang and Aldrin-Kirk, Patrick and Cardoso, Tiago and Nolbrant, Sara and Hartnor, Morgan and Mudannayake, Janitha and Parmar, Malin and Björklund, Tomas}},
  issn         = {{1091-6490}},
  language     = {{eng}},
  month        = {{12}},
  number       = {{52}},
  pages        = {{27053--27062}},
  publisher    = {{National Academy of Sciences}},
  series       = {{Proceedings of the National Academy of Sciences of the United States of America}},
  title        = {{A systematic capsid evolution approach performed in vivo for the design of AAV vectors with tailored properties and tropism}},
  url          = {{https://lup.lub.lu.se/search/files/73074708/Davidsson_in_PNAS_191212.pdf}},
  doi          = {{10.1073/pnas.1910061116}},
  volume       = {{116}},
  year         = {{2019}},
}