PMID- 35173619
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220219
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 13
DP  - 2022
TI  - Chimeric Mice Engrafted With Canine Hepatocytes Exhibits Similar AAV Transduction 
      Efficiency to Hemophilia B Dog.
PG  - 815317
LID - 10.3389/fphar.2022.815317 [doi]
LID - 815317
AB  - Adeno-associated virus (AAV) mediated gene therapy has been successfully applied 
      in clinical trials, including hemophilia. Novel AAV vectors have been developed 
      with enhanced transduction and specific tissue tropism. Considering the 
      difference in efficacy of AAV transduction between animal models and patients, 
      the chimeric xenograft mouse model with human hepatocytes has unique advantages 
      of studying AAV transduction efficiency in human hepatocytes. However, it is 
      unclear whether the results in humanized mice can predict AAV transduction 
      efficiency in human hepatocytes. To address this issue, we studied the AAV 
      transduction efficacy in canine hepatocytes in both canine hepatocyte xenografted 
      mice and real dogs. After administration of AAV vectors from different serotypes 
      into canine hepatocyte xenograft mice, AAV8 induced the best canine hepatocyte 
      transduction followed by AAV9, then AAV3, 7, 5 and 2. After administration of 
      AAV/cFIX (cFIX-opt-R338L) vectors in hemophilia B dogs, consistent with the 
      result in chimeric mice, AAV8 induced the highest cFIX protein expression and 
      function, followed by AAV9 and then AAV2. These results suggest that mice 
      xenografted with hepatocytes from different species could be used to predict the 
      AAV liver transduction in real species and highlight this potential platform to 
      explore novel AAV variants for future clinical applications.
CI  - Copyright (c) 2022 Shao, Sun, Chen, Dobbins, Merricks, Samulski, Nichols and Li.
FAU - Shao, Wenwei
AU  - Shao W
AD  - Academy of Medical Engineering and Translational Medicine, Tianjin University, 
      Tianjin, China.
AD  - Gene Therapy Center, University of North Carolina at Chapel Hill, Chapel Hill, 
      NC, United States.
FAU - Sun, Junjiang
AU  - Sun J
AD  - Gene Therapy Center, University of North Carolina at Chapel Hill, Chapel Hill, 
      NC, United States.
AD  - Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of 
      Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, United 
      States.
FAU - Chen, Xiaojing
AU  - Chen X
AD  - Gene Therapy Center, University of North Carolina at Chapel Hill, Chapel Hill, 
      NC, United States.
FAU - Dobbins, Amanda
AU  - Dobbins A
AD  - Gene Therapy Center, University of North Carolina at Chapel Hill, Chapel Hill, 
      NC, United States.
FAU - Merricks, Elizabeth P
AU  - Merricks EP
AD  - Department of Pathology and Laboratory Medicine and The Blood Research Center, 
      University of North Carolina at Chapel Hill, Chapel Hill, NC, United States.
FAU - Samulski, R Jude
AU  - Samulski RJ
AD  - Gene Therapy Center, University of North Carolina at Chapel Hill, Chapel Hill, 
      NC, United States.
AD  - Department of Pharmacology, School of Medicine, University of North Carolina at 
      Chapel Hill, Chapel Hill, NC, United States.
FAU - Nichols, Timothy C
AU  - Nichols TC
AD  - Department of Pathology and Laboratory Medicine and The Blood Research Center, 
      University of North Carolina at Chapel Hill, Chapel Hill, NC, United States.
FAU - Li, Chengwen
AU  - Li C
AD  - Gene Therapy Center, University of North Carolina at Chapel Hill, Chapel Hill, 
      NC, United States.
AD  - Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel 
      Hill, NC, United States.
AD  - Carolina Institute for Developmental Disabilities, University of North Carolina 
      at Chapel Hill, Chapel Hill, NC, United States.
LA  - eng
PT  - Journal Article
DEP - 20220131
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC8841897
OTO - NOTNLM
OT  - AAV (Adeno-associated virus)
OT  - canine hepatocytes
OT  - chimeric mice
OT  - hemophilia B
OT  - liver transduction
COIS- CL is a cofounder of Bedrock Therapeutics, Nabgen and GeneVentiv, Inc. He has 
      licensed patents by UNC and has received royalties from these startups and 
      Asklepios Biopharmaceutical. RS is the founder and a shareholder at Asklepios 
      BioPharmaceutical. He holds patents that have been licensed by UNC to Asklepios 
      Biopharmaceutical, for which he receives royalties. He has consulted for Baxter 
      Healthcare and has received payment for speaking. The remaining authors declare 
      that the research was conducted in the absence of any commercial or financial 
      relationships that could be construed as a potential conflict of interest.
EDAT- 2022/02/18 06:00
MHDA- 2022/02/18 06:01
PMCR- 2022/01/31
CRDT- 2022/02/17 05:34
PHST- 2021/11/24 00:00 [received]
PHST- 2022/01/17 00:00 [accepted]
PHST- 2022/02/17 05:34 [entrez]
PHST- 2022/02/18 06:00 [pubmed]
PHST- 2022/02/18 06:01 [medline]
PHST- 2022/01/31 00:00 [pmc-release]
AID - 815317 [pii]
AID - 10.3389/fphar.2022.815317 [doi]
PST - epublish
SO  - Front Pharmacol. 2022 Jan 31;13:815317. doi: 10.3389/fphar.2022.815317. 
      eCollection 2022.