PMID- 11899074
OWN - NLM
STAT- MEDLINE
DCOM- 20020625
LR  - 20190922
IS  - 1566-5240 (Print)
IS  - 1566-5240 (Linking)
VI  - 1
IP  - 2
DP  - 2001 May
TI  - Adeno-associated virus (AAV) as a vehicle for therapeutic gene delivery: 
      improvements in vector design and viral production enhance potential to prolong 
      graft survival in pancreatic islet cell transplantation for the reversal of type 
      1 diabetes.
PG  - 245-58
AB  - Most viral gene delivery syslems utilized to date have demonstrated significant 
      limitations in practicality and safety due to the level and duration of 
      recombinant transgene expression as well as their induction of host 
      immunogenicity to vector proteins. Recombinant adeno-associated virus (rAAV) 
      vectors appear to offer a vehicle for safe, long-term therapeutic gene transfer; 
      factors afforded through the propensity of rAAV to establish long-term latency 
      without deleterious effects on the host cell and the relative non-immunogenicity 
      of the virus or viral expressed transgenes. The principal historical limitation 
      of this vector system, efficiency of rAAV-mediated transduction, has recently 
      observed a dramatic increase as the titer, purity, and production capacity of 
      rAAV preparations have improved. In terms of systems that could benefit from such 
      improvements, rAAV gene therapy to enhance solid organ transplantation would 
      appear an obvious choice with islet transplantation forming a promising candidate 
      due to the ability to perform viral transductions ex vivo. Currently, islet 
      transplantation can be used to treat type 1 diabetes yet persisting alloimmune 
      and autoimmune responses represent major obstacles to the clinical success for 
      this procedure. The delivery of transgenes capable of interfering with antigenic 
      recognition and/or cell death [e.g., Fas ligand (FasL), Bcl-2, Bcl-XL] as well as 
      imparting tolerance/immunoregulation [e.g., interleukin(IL)-4, IL-10, 
      transforming growth factor (TGF)-beta], or cytoprotection [e.g., heme oxygenase-1 
      (HO-1), catalase, manganese superoxide dismutase (MnSOD)] may prevent recurrent 
      type 1 diabetes in islet transplantation and offer a promising form of 
      immunotherapy. Research investigations utilizing such systems may also provide 
      information vital to understanding the immunoregulatory mechanisms critical to 
      the development of both alloimmune and autoimmune islet cell rejection mechanisms 
      and recurrent type 1 diabetes.
FAU - Kapturczak, M H
AU  - Kapturczak MH
AD  - Department of Medicine, University of Florida, Gainesville 32610, USA.
FAU - Flotte, T
AU  - Flotte T
FAU - Atkinson, M A
AU  - Atkinson MA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PT  - Review
PL  - Netherlands
TA  - Curr Mol Med
JT  - Current molecular medicine
JID - 101093076
SB  - IM
MH  - Animals
MH  - Autoimmunity
MH  - Combined Modality Therapy
MH  - Dependovirus/*genetics
MH  - Diabetes Mellitus, Type 1/immunology/*therapy
MH  - *Gene Transfer Techniques
MH  - Genes, Reporter
MH  - *Genetic Therapy
MH  - Genetic Vectors
MH  - *Graft Survival
MH  - Humans
MH  - *Islets of Langerhans Transplantation
MH  - Transgenes
MH  - Transplantation, Homologous
RF  - 164
EDAT- 2002/03/20 10:00
MHDA- 2002/06/26 10:01
CRDT- 2002/03/20 10:00
PHST- 2002/03/20 10:00 [pubmed]
PHST- 2002/06/26 10:01 [medline]
PHST- 2002/03/20 10:00 [entrez]
AID - 10.2174/1566524013363979 [doi]
PST - ppublish
SO  - Curr Mol Med. 2001 May;1(2):245-58. doi: 10.2174/1566524013363979.