scholarly journals Hoechst increases adeno-associated virus-mediated transgene expression in airway epithelia by inducing the cytomegalovirus promoter

2012 ◽  
Vol 14 (6) ◽  
pp. 366-373 ◽  
Author(s):  
David D. Dickey ◽  
Katherine J. D. A. Excoffon ◽  
Krista R. Young ◽  
Kalpaj R. Parekh ◽  
Joseph Zabner
Keyword(s):  
Transgene Expression ◽  
Airway Epithelia ◽  
Adeno Associated Virus ◽  
Cytomegalovirus Promoter

scholarly journals Evading the AAV Immune Response in Mucopolysaccharidoses

2020 ◽  
Vol 21 (10) ◽  
pp. 3433
Author(s):  
Matthew Piechnik ◽  
Kazuki Sawamoto ◽  
Hidenori Ohnishi ◽  
Norio Kawamoto ◽  
Yasuhiko Ago ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Immune Response ◽  
Humoral Immune Response ◽  
Transgene Expression ◽  
Evidence Based ◽  
Adeno Associated Virus ◽  
Gene Therapies ◽  
Humoral Immune ◽  
Significant Challenge ◽  
Racial Background

The humoral immune response elicited by adeno-associated virus (AAV)-mediated gene therapy for the treatment of mucopolysaccharidoses (MPS) poses a significant challenge to achieving therapeutic levels of transgene expression. Antibodies targeting the AAV capsid as well as the transgene product diminish the production of glycosaminoglycan (GAG)-degrading enzymes essential for the treatment of MPS. Patients who have antibodies against AAV capsid increase in number with age, serotype, and racial background and are excluded from the clinical trials at present. In addition, patients who have undergone AAV gene therapy are often excluded from the additional AAV gene therapy with the same serotype, since their acquired immune response (antibody) against AAV will limit further efficacy of treatment. Several methods are being developed to overcome this immune response, such as novel serotype design, antibody reduction by plasmapheresis and immunosuppression, and antibody evasion using empty capsids and enveloped AAV vectors. In this review, we examine the mechanisms of the anti-AAV humoral immune response and evaluate the strengths and weaknesses of current evasion strategies in order to provide an evidence-based recommendation on evading the immune response for future AAV-mediated gene therapies for MPS.

scholarly journals Five Years of Successful Inducible Transgene Expression Following Locoregional Adeno-Associated Virus Delivery in Nonhuman Primates with No Detectable Immunity

2019 ◽  
Vol 30 (7) ◽  
pp. 802-813 ◽  
Author(s):  
Mickaël Guilbaud ◽  
Marie Devaux ◽  
Celia Couzinié ◽  
Johanne Le Duff ◽  
Alice Toromanoff ◽  
...  
Keyword(s):  
Transgene Expression ◽  
Nonhuman Primates ◽  
Adeno Associated Virus ◽  
Virus Delivery

One year transgene expression with adeno-associated virus cardiac gene transfer

2005 ◽  
Vol 100 (3) ◽  
pp. 421-426 ◽  
Author(s):  
Y. Joseph Woo ◽  
Janet C.L. Zhang ◽  
Matthew D. Taylor ◽  
Jeffrey E. Cohen ◽  
Vivian M. Hsu ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Transgene Expression ◽  
Adeno Associated Virus ◽  
Cardiac Gene ◽  
One Year

scholarly journals Lack of Repeat Transduction by Recombinant Adeno-Associated Virus Type 5/5 Vectors in the Mouse Airway

2007 ◽  
Vol 81 (22) ◽  
pp. 12360-12367 ◽  
Author(s):  
Stephanie G. Sumner-Jones ◽  
Deborah R. Gill ◽  
Stephen C. Hyde
Keyword(s):  
Transgene Expression ◽  
Lung Diseases ◽  
Repeated Administration ◽  
Transduction Efficiency ◽  
Viral Gene ◽  
Rapid Rise ◽  
Adeno Associated Virus ◽  
Subsequent Failure

ABSTRACT While recombinant adeno-associated virus (rAAV) vectors promote long-term transgene expression in the lungs and other organs, the goal of correcting chronic inherited lung diseases such as cystic fibrosis with this type of viral gene transfer vector is limited by the requirement of achieving stable potent transgene expression, potentially requiring vector readministration. Here we evaluated the abilities of rAAV type 5/5 (rAAV5/5) vectors based on the genome and capsid of AAV5 to efficiently transduce the lungs and nasal epithelium of mice after repeated administration. Transduction efficiency as judged by reporter gene expression was markedly reduced on a second rAAV5/5 administration and effectively abolished on a third. Varying the period between administrations from 8 to 36 weeks did not allow efficient repeated administration. A rapid rise in anti-AAV5 antibodies was noted after rAAV5/5 vector administration that was sustained for the entire period of investigation (in some cases exceeding 9 months). Furthermore, this antibody response and subsequent failure to repeatedly administer the vector were not rescued by the in vivo expression of CTLA4Ig from an rAAV5/5 vector. These results suggest that without the development of an effective and clinically acceptable immunosuppression strategy, treatments for chronic diseases that require repeated administration of rAAV5/5 vectors will be unsuccessful.

THU-363-Lipid nanoparticle pre-treatment improves adeno-associated virus diffusion in the primate liver and enables an increase of therapeutic transgene expression

2019 ◽  
Vol 70 (1) ◽  
pp. e313-e314
Author(s):  
Karin L Kwikkers ◽  
Lukas Schwarz ◽  
Johannes de Laat ◽  
Anna Majowicz ◽  
Paula S. Miranda ◽  
...  
Keyword(s):  
Transgene Expression ◽  
Adeno Associated Virus ◽  
Lipid Nanoparticle ◽  
Pre Treatment
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