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Marcus Davidsson

Marcus Davidsson

Postdoctoral fellow

Marcus Davidsson

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

Author

  • Marcus Davidsson
  • Gang Wang
  • Patrick Aldrin-Kirk
  • Tiago Cardoso
  • Sara Nolbrant
  • Morgan Hartnor
  • Janitha Mudannayake
  • Malin Parmar
  • Tomas Björklund

Summary, in English

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.

Department/s

  • Molecular Neuromodulation
  • StemTherapy: National Initiative on Stem Cells for Regenerative Therapy
  • Developmental and Regenerative Neurobiology
  • MultiPark: Multidisciplinary research focused on Parkinson´s disease

Publishing year

2019-12-26

Language

English

Pages

27053-27062

Publication/Series

Proceedings of the National Academy of Sciences of the United States of America

Volume

116

Issue

52

Document type

Journal article

Publisher

National Acad Sciences

Topic

  • Neurosciences

Status

Published

Research group

  • Molecular Neuromodulation
  • Developmental and Regenerative Neurobiology

ISBN/ISSN/Other

  • ISSN: 1091-6490