A systematic capsid evolution approach performed in vivo for the design of AAV vectors with tailored properties and tropism
(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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- author
- Davidsson, Marcus LU ; Wang, Gang LU ; Aldrin-Kirk, Patrick LU ; Cardoso, Tiago LU ; Nolbrant, Sara LU ; Hartnor, Morgan ; Mudannayake, Janitha LU ; Parmar, Malin LU and Björklund, Tomas LU
- organization
- publishing date
- 2019-12-26
- 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
-
- scopus:85077269512
- pmid:31818949
- 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
- 2024-09-18 15:26:58
@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}}, }