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A systematic capsid...
A systematic capsid evolution approach performed in vivo for the design of AAV vectors with tailored properties and tropism
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- Davidsson, Marcus (författare)
- Lund University,Lunds universitet,Molekylär neuromodulering,Forskargrupper vid Lunds universitet,Molecular Neuromodulation,Lund University Research Groups
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- Wang, Gang (författare)
- Lund University,Lunds universitet,Molekylär neuromodulering,Forskargrupper vid Lunds universitet,Molecular Neuromodulation,Lund University Research Groups
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- Aldrin-Kirk, Patrick (författare)
- Lund University,Lunds universitet,Molekylär neuromodulering,Forskargrupper vid Lunds universitet,Molecular Neuromodulation,Lund University Research Groups
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- Cardoso, Tiago (författare)
- Lund University,Lunds universitet,Utvecklings- och regenerativ neurobiologi,Forskargrupper vid Lunds universitet,Developmental and Regenerative Neurobiology,Lund University Research Groups
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- Nolbrant, Sara (författare)
- Lund University,Lunds universitet,Utvecklings- och regenerativ neurobiologi,Forskargrupper vid Lunds universitet,Developmental and Regenerative Neurobiology,Lund University Research Groups
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- Hartnor, Morgan (författare)
- Lund University
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- Mudannayake, Janitha (författare)
- Lund University,Lunds universitet,Molekylär neuromodulering,Forskargrupper vid Lunds universitet,Utvecklings- och regenerativ neurobiologi,Molecular Neuromodulation,Lund University Research Groups,Developmental and Regenerative Neurobiology
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- Parmar, Malin (författare)
- Lund University,Lunds universitet,Utvecklings- och regenerativ neurobiologi,Forskargrupper vid Lunds universitet,Developmental and Regenerative Neurobiology,Lund University Research Groups
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- Björklund, Tomas (författare)
- Lund University,Lunds universitet,Molekylär neuromodulering,Forskargrupper vid Lunds universitet,Molecular Neuromodulation,Lund University Research Groups
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(creator_code:org_t)
- 2019-12-09
- 2019
- Engelska 10 s.
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 116:52, s. 27053-27062
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http://dx.doi.org/10... (free)
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
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