PMID- 37074875
OWN - NLM
STAT- MEDLINE
DCOM- 20230421
LR  - 20240212
IS  - 2471-254X (Electronic)
IS  - 2471-254X (Linking)
VI  - 7
IP  - 2
DP  - 2023 Feb 1
TI  - A multiplexed barcode approach to simultaneously evaluate gene delivery by 
      adeno-associated virus capsid variants in nonhuman primates.
PG  - e0009
LID - 10.1097/HC9.0000000000000009 [doi]
LID - e0009
AB  - BACKGROUND AND AIMS: Adeno-associated virus (AAV) vectors are widely used to 
      deliver therapeutic transgenes to distinct tissues, including the liver. Vectors 
      based on naturally occurring AAV serotypes as well as vectors using engineered 
      capsids have shown variations in tissue tropism and level of transduction between 
      different mouse models. Moreover, results obtained in rodents frequently lack 
      translatability into large animal studies. In light of the increasing interest in 
      AAV vectors for human gene therapy, an increasing number of studies are being 
      performed in nonhuman primates. To keep animal numbers to a minimum and thus 
      optimize the process of AAV capsid selection, we developed a multiplex barcoding 
      approach to simultaneously evaluate the in vivo vector performance for a set of 
      serotypes and capsid-engineered AAV vectors across multiple organs. APPROACH AND 
      RESULTS: Vector biodistribution and transgene expression were assessed by 
      quantitative PCR, quantitative reverse transcription PCR, vector DNA amplicon 
      Illumina sequencing and vRNAseq in male and female rhesus macaques simultaneously 
      dosed with a mixture of barcoded naturally occurring or engineered AAV vectors 
      encoding the same transgene. As expected, our findings show animal-to-animal 
      variation in both the biodistribution and tissue transduction pattern, which was 
      partly influenced by each animal's distinctive serological status. CONCLUSIONS: 
      This method offers a robust approach to AAV vector optimization that can be used 
      to identify and validate AAV vectors for gene delivery to potentially any 
      anatomical site or cell type.
CI  - Copyright (c) 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on 
      behalf of the American Association for the Study of Liver Diseases.
FAU - Stone, Daniel
AU  - Stone D
AUID- ORCID: 0000-0003-1619-7541
AD  - Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, 
      Washington, USA.
FAU - Meumann, Nadja
AU  - Meumann N
AUID- ORCID: 0000-0003-4929-249
AD  - Institute of Experimental Hematology, Hannover Medical School, Hannover, Germany.
FAU - Kuhlmann, Anne-Sophie
AU  - Kuhlmann AS
AD  - Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, Washington, 
      USA.
FAU - Peterson, Christopher W
AU  - Peterson CW
AUID- ORCID: 0000-0002-3215-8924
AD  - Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, Washington, 
      USA.
AD  - Department of Medicine, University of Washington, Seattle, USA.
FAU - Xie, Hong
AU  - Xie H
AUID- ORCID: 0000-0001-6610-0723
AD  - Department of Laboratory Medicine and Pathology, University of Washington, 
      Seattle, USA.
FAU - Roychoudhury, Pavitra
AU  - Roychoudhury P
AUID- ORCID: 0000-0002-4567-8232
AD  - Department of Laboratory Medicine and Pathology, University of Washington, 
      Seattle, USA.
FAU - Loprieno, Michelle A
AU  - Loprieno MA
AUID- ORCID: 0000-0002-2905-485
AD  - Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, 
      Washington, USA.
FAU - Vu, Xuan-Khang
AU  - Vu XK
AD  - Institute of Experimental Hematology, Hannover Medical School, Hannover, Germany.
FAU - Strongin, Daniel E
AU  - Strongin DE
AUID- ORCID: 0000-0002-5015-9816
AD  - Department of Laboratory Medicine and Pathology, University of Washington, 
      Seattle, USA.
FAU - Kenkel, Elizabeth J
AU  - Kenkel EJ
AD  - Department of Laboratory Medicine and Pathology, University of Washington, 
      Seattle, USA.
FAU - Haick, Anoria
AU  - Haick A
AD  - Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, 
      Washington, USA.
FAU - Stensland, Laurence
AU  - Stensland L
AD  - Department of Laboratory Medicine and Pathology, University of Washington, 
      Seattle, USA.
FAU - Obenza, Willimark M
AU  - Obenza WM
AD  - Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, Washington, 
      USA.
FAU - Parrott, Jacob
AU  - Parrott J
AD  - Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, Washington, 
      USA.
FAU - Nelson, Veronica
AU  - Nelson V
AUID- ORCID: 0000-0003-4309-6236
AD  - Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, Washington, 
      USA.
FAU - Murnane, Robert D
AU  - Murnane RD
AD  - Washington National Primate Research Center, University of Washington, Seattle, 
      Washington, USA.
FAU - Huang, Meei-Li
AU  - Huang ML
AUID- ORCID: 0000-0003-2058-2776
AD  - Department of Laboratory Medicine and Pathology, University of Washington, 
      Seattle, USA.
FAU - Aubert, Martine
AU  - Aubert M
AUID- ORCID: 0000-0003-1125-6856
AD  - Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, 
      Washington, USA.
FAU - Kiem, Hans-Peter
AU  - Kiem HP
AUID- ORCID: 0000-0001-5949-4947
AD  - Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, 
      Washington, USA.
AD  - Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, Washington, 
      USA.
AD  - Department of Medicine, University of Washington, Seattle, USA.
AD  - Washington National Primate Research Center, University of Washington, Seattle, 
      Washington, USA.
FAU - Buning, Hildegard
AU  - Buning H
AUID- ORCID: 0000-0002-3365-6933
AD  - Institute of Experimental Hematology, Hannover Medical School, Hannover, Germany.
FAU - Jerome, Keith R
AU  - Jerome KR
AUID- ORCID: 0000-0002-8212-3789
AD  - Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, 
      Washington, USA.
AD  - Department of Laboratory Medicine and Pathology, University of Washington, 
      Seattle, USA.
LA  - eng
GR  - P30 AI027757/AI/NIAID NIH HHS/United States
GR  - P30 CA015704/CA/NCI NIH HHS/United States
GR  - UM1 AI126623/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20230120
PL  - United States
TA  - Hepatol Commun
JT  - Hepatology communications
JID - 101695860
RN  - 0 (Capsid Proteins)
SB  - IM
MH  - Animals
MH  - Mice
MH  - Female
MH  - Male
MH  - Humans
MH  - *Capsid/metabolism
MH  - *Dependovirus/genetics/metabolism
MH  - Tissue Distribution
MH  - Macaca mulatta/genetics/metabolism
MH  - Capsid Proteins/genetics/metabolism
MH  - Genetic Therapy/methods
PMC - PMC10503678
COIS- A.S.K. consults for Immusoft. N.M. and H.B. are inventors of a patent describing 
      AAV capsids MLIV.A and MLIV.K (WO/2020/193799A1). K.R.J. own stocks in, consults 
      for, and received grants from Excision Biotherapeutics. K.R.J. has a sponsored 
      research agreement with Emendo Biotherapeutics. D.S. and M.A. have sponsored 
      research agreements with Excision Biotherapeutics. For the remaining authors 
      nothing to report.
EDAT- 2023/04/19 18:42
MHDA- 2023/04/21 06:41
PMCR- 2023/01/20
CRDT- 2023/04/19 12:23
PHST- 2022/08/24 00:00 [received]
PHST- 2022/09/21 00:00 [accepted]
PHST- 2023/04/21 06:41 [medline]
PHST- 2023/04/19 18:42 [pubmed]
PHST- 2023/04/19 12:23 [entrez]
PHST- 2023/01/20 00:00 [pmc-release]
AID - 02009842-202302010-00011 [pii]
AID - 10.1097/HC9.0000000000000009 [doi]
PST - epublish
SO  - Hepatol Commun. 2023 Jan 20;7(2):e0009. doi: 10.1097/HC9.0000000000000009. 
      eCollection 2023 Feb 1.