PMID- 32253938
OWN - NLM
STAT- MEDLINE
DCOM- 20210823
LR  - 20210823
IS  - 1557-7422 (Electronic)
IS  - 1043-0342 (Print)
IS  - 1043-0342 (Linking)
VI  - 31
IP  - 9-10
DP  - 2020 May
TI  - Adeno-Associated Virus and Hematopoietic Stem Cells: The Potential of 
      Adeno-Associated Virus Hematopoietic Stem Cells in Genetic Medicines.
PG  - 542-552
LID - 10.1089/hum.2020.049 [doi]
AB  - Adeno-associated virus (AAV)-based vectors have transformed into powerful 
      elements of genetic medicine with proven therapeutic efficacy and a good safety 
      profile. Over the years, efforts to transduce hematopoietic stem cells (HSCs) 
      with AAV2 vectors have, however, been challenging. While there was evidence that 
      AAV2 delivered vector genomes to primitive, quiescent, multipotential, 
      self-renewing, in vivo engrafting HSCs, transgene expression was elusive. In this 
      study, we review the evolution of AAV transduction of HSC, starting with AAV2 
      vectors leading to the isolation of a family of naturally occurring AAVs from 
      human CD34(+) HSC, the AAVHSC. The stem cell-derived AAVHSCs have turned out to 
      have remarkable potentials for genetic therapies well beyond the hematopoietic 
      system. AAVHSCs have tropism for a wide variety of peripheral tissues, including 
      the liver, muscle, and the retina. They cross the blood-brain barrier and 
      transduce cells of the central nervous system. Preclinical gene therapy studies 
      underway using AAVHSC vectors are discussed. We review the notable ability of 
      AAVHSCs to mediate efficient, seamless homologous recombination in the absence of 
      exogenous nuclease activity and discuss the therapeutic implications. We also 
      discuss early results from an AAVHSC-based clinical gene therapy trial that is 
      underway for the treatment of phenylketonuria. Thus, the stem cell-derived 
      AAVHSC, offer a multifaceted platform for in vivo gene therapy and genome editing 
      for the treatment of inherited diseases.
FAU - Chatterjee, Saswati
AU  - Chatterjee S
AD  - Department of Surgery, Beckman Research Institute of City of Hope Medical Center, 
      Duarte, California, USA.
FAU - Sivanandam, Venkatesh
AU  - Sivanandam V
AD  - Department of Surgery, Beckman Research Institute of City of Hope Medical Center, 
      Duarte, California, USA.
FAU - Wong, Kamehameha Kai-Min , Jr
AU  - Wong KK , Jr
AD  - Department of Hematology and Stem Cell Transplantation, City of Hope Medical 
      Center, Duarte, California, USA.
LA  - eng
GR  - N01AI40001/AI/NIAID NIH HHS/United States
GR  - R01 HL087285/HL/NHLBI NIH HHS/United States
GR  - P30 CA033572/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - United States
TA  - Hum Gene Ther
JT  - Human gene therapy
JID - 9008950
SB  - IM
MH  - Animals
MH  - Dependovirus/*genetics
MH  - *Gene Editing
MH  - *Genetic Therapy
MH  - Hematopoietic Stem Cells/*metabolism/*virology
MH  - Humans
MH  - Leukodystrophy, Metachromatic/genetics/therapy
MH  - Phenylketonurias/genetics/therapy
MH  - Transduction, Genetic
MH  - Transgenes
PMC - PMC7232699
OTO - NOTNLM
OT  - AAV
OT  - AAVHSC
OT  - PKU
OT  - gene editing
OT  - gene therapy
OT  - hematopoietic stem cells
COIS- S.C. is a co-founder of, has equity in, and serves on the scientific advisory 
      board of Homology Medicines Inc., K.K.W. has equity in Homology Medicines, Inc.
EDAT- 2020/04/08 06:00
MHDA- 2021/08/24 06:00
PMCR- 2021/05/01
CRDT- 2020/04/08 06:00
PHST- 2020/04/08 06:00 [pubmed]
PHST- 2021/08/24 06:00 [medline]
PHST- 2020/04/08 06:00 [entrez]
PHST- 2021/05/01 00:00 [pmc-release]
AID - 10.1089/hum.2020.049 [pii]
AID - 10.1089/hum.2020.049 [doi]
PST - ppublish
SO  - Hum Gene Ther. 2020 May;31(9-10):542-552. doi: 10.1089/hum.2020.049.