PMID- 31818949
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20221205
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 116
IP  - 52
DP  - 2019 Dec 26
TI  - A systematic capsid evolution approach performed in vivo for the design of AAV 
      vectors with tailored properties and tropism.
PG  - 27053-27062
LID - 10.1073/pnas.1910061116 [doi]
AB  - 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.
FAU - Davidsson, Marcus
AU  - Davidsson M
AD  - Molecular Neuromodulation, Department of Experimental Medical Science, Lund 
      University, 221 84 Lund, Sweden.
FAU - Wang, Gang
AU  - Wang G
AD  - Molecular Neuromodulation, Department of Experimental Medical Science, Lund 
      University, 221 84 Lund, Sweden.
FAU - Aldrin-Kirk, Patrick
AU  - Aldrin-Kirk P
AD  - Molecular Neuromodulation, Department of Experimental Medical Science, Lund 
      University, 221 84 Lund, Sweden.
FAU - Cardoso, Tiago
AU  - Cardoso T
AD  - Developmental and Regenerative Neurobiology, Department of Experimental Medical 
      Science, Lund Stem Cell Center, Lund University, 221 84 Lund, Sweden.
FAU - Nolbrant, Sara
AU  - Nolbrant S
AD  - Developmental and Regenerative Neurobiology, Department of Experimental Medical 
      Science, Lund Stem Cell Center, Lund University, 221 84 Lund, Sweden.
FAU - Hartnor, Morgan
AU  - Hartnor M
AD  - Molecular Neuromodulation, Department of Experimental Medical Science, Lund 
      University, 221 84 Lund, Sweden.
FAU - Mudannayake, Janitha
AU  - Mudannayake J
AD  - Molecular Neuromodulation, Department of Experimental Medical Science, Lund 
      University, 221 84 Lund, Sweden.
FAU - Parmar, Malin
AU  - Parmar M
AD  - Developmental and Regenerative Neurobiology, Department of Experimental Medical 
      Science, Lund Stem Cell Center, Lund University, 221 84 Lund, Sweden.
FAU - Bjorklund, Tomas
AU  - Bjorklund T
AUID- ORCID: 0000-0001-7968-0034
AD  - Molecular Neuromodulation, Department of Experimental Medical Science, Lund 
      University, 221 84 Lund, Sweden.
LA  - eng
PT  - Journal Article
DEP - 20191209
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
SB  - IM
PMC - PMC6936499
OTO - NOTNLM
OT  - barcoding
OT  - dopamine
OT  - gene therapy
OT  - retrograde transport
OT  - vector evolution
COIS- Competing interest statement: M.D. and T.B. are authors of a patent application 
      covering components of the presented study.
EDAT- 2019/12/11 06:00
MHDA- 2019/12/11 06:01
PMCR- 2019/12/09
CRDT- 2019/12/11 06:00
PHST- 2019/12/11 06:00 [pubmed]
PHST- 2019/12/11 06:01 [medline]
PHST- 2019/12/11 06:00 [entrez]
PHST- 2019/12/09 00:00 [pmc-release]
AID - 1910061116 [pii]
AID - 201910061 [pii]
AID - 10.1073/pnas.1910061116 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2019 Dec 26;116(52):27053-27062. doi: 
      10.1073/pnas.1910061116. Epub 2019 Dec 9.