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

scholarly journals Lack of an Immune Response against the Tetracycline-Dependent Transactivator Correlates with Long-Term Doxycycline-Regulated Transgene Expression in Nonhuman Primates after Intramuscular Injection of Recombinant Adeno-Associated Virus

2002 ◽  
Vol 76 (22) ◽  
pp. 11605-11611 ◽  
Author(s):  
David Favre ◽  
Véronique Blouin ◽  
Nathalie Provost ◽  
Radec Spisek ◽  
Françoise Porrot ◽  
...  
Keyword(s):  
Transgene Expression ◽  
Nonhuman Primates ◽  
Cynomolgus Macaque ◽  
Experimental Period ◽  
Adeno Associated Virus ◽  
Cellular Immune Responses ◽  
Transactivator Protein ◽  
Cellular Immune ◽  
Vector Dna

ABSTRACT We previously documented persistent regulation of erythropoietin (Epo) secretion in mice after a single intramuscular (i.m.) injection of a recombinant adeno-associated virus (rAAV) vector harboring both the tetracycline-dependent transactivator (rtTA) and the Epo cDNA (D. Bohl, A. Salvetti, P. Moullier, and J. M. Heard, Blood 92:1512-1517, 1998). Using the same vector harboring the cynomolgus macaque Epo cDNA instead, the present study evaluated the ability of the tetracycline-regulatable (tetR) system to establish long-term transgene regulation in nonhuman primates. The vector was administered i.m., after which 5-day induction pulses were performed monthly for up to 13 months by using doxycycline (DOX), a tetracycline analog. We show that initial inductions were successful in all individuals and that there was a tight regulation and a rapid deinduction pattern upon DOX withdrawal. For one macaque, regulation of Epo secretion was maintained during the entire experimental period; for the five remaining macaques, secreted Epo became indistinguishable from endogenous Epo upon repeated DOX inductions. We investigated the mechanism involved and showed that, except in the animal in which secretion persisted, delayed humoral and cellular immune responses were directed against the rtTA transactivator protein associated with the reduction of vector DNA in transduced muscles. This study provides some evidence that, when the immune system is not mobilized against the rtTA transactivator, the tetR-regulatable system is able to support long-term transgene regulation in the context of an rAAV in nonhuman primates. In addition, our results suggest potential improvements for vector design.

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.

Schwannoma gene therapy by adeno-associated virus delivery of the pore-forming protein Gasdermin-D

2019 ◽  
Vol 26 (9-10) ◽  
pp. 259-267 ◽  
Author(s):  
Sherif G. Ahmed ◽  
Ahmed Abdelanabi ◽  
Mohamed Doha ◽  
Gary J. Brenner
Keyword(s):  
Gene Therapy ◽  
Adeno Associated Virus ◽  
Virus Delivery

Biomaterial-Guided Recombinant Adeno-associated Virus Delivery from Poly(Sodium Styrene Sulfonate)-Grafted Poly(ɛ-Caprolactone) Films to Target Human Bone Marrow Aspirates

2020 ◽  
Vol 26 (7-8) ◽  
pp. 450-459 ◽  
Author(s):  
Jagadeesh K. Venkatesan ◽  
Céline Falentin-Daudré ◽  
Amélie Leroux ◽  
Véronique Migonney ◽  
Magali Cucchiarini
Keyword(s):  
Bone Marrow ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Adeno Associated Virus ◽  
Styrene Sulfonate ◽  
Sodium Styrene Sulfonate ◽  
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
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