Overcoming the Host Immune Response to Adeno-Associated Virus Gene Delivery Vectors: The Race Between Clearance, Tolerance, Neutralization, and Escape

Immune responses in gene therapy with adeno-associated virus (AAV) vectors have been the object of almost two decades of study. Although preclinical models helped to define and predict certain aspects of interactions between the vector and the host immune system, most of our current knowledge has co...

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Bibliographic Details
Published inAnnual review of virology Vol. 4; no. 1; pp. 511 - 534
Main Authors Mingozzi, Federico, High, Katherine A
Format Journal Article
LanguageEnglish
Published United States Annual Reviews 29.09.2017
Annual Review
Subjects
AAV
Animals
Antibodies, Neutralizing - adverse effects
Antibodies, Neutralizing - biosynthesis
Antibodies, Neutralizing - immunology
Dependovirus - genetics
Dependovirus - immunology
gene therapy
Gene Transfer Techniques
Genetic Therapy
Genetic Vectors - adverse effects
Humans
Immune Tolerance
Immunity, Active
immunomonitoring
immunotoxicity
Life Sciences
Mice
neutralizing antibodies
tolerance
immunomonitoring
gene therapy
immunotoxicity
neutralizing antibodies
AAV
tolerance
Gene Transfer Techniques
Genetic Therapy
Active
Animals
Dependovirus/genetics/immunology
Genetic Vectors/adverse effects
Humans
Immune Tolerance
Antibodies
Neutralizing/adverse effects/biosynthesis/immunology
Mice
Immunity
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Summary:Immune responses in gene therapy with adeno-associated virus (AAV) vectors have been the object of almost two decades of study. Although preclinical models helped to define and predict certain aspects of interactions between the vector and the host immune system, most of our current knowledge has come from clinical trials. These studies have allowed development of effective interventions for modulating immunotoxicities associated with vector administration, resulting in therapeutic advances. However, the road to full understanding and effective modulation of immune responses in gene therapy is still long; the determinants of the balance between tolerance and immunogenicity in AAV vector-mediated gene transfer are not fully understood, and effective solutions for overcoming preexisting neutralizing antibodies are still lacking. However, despite these challenges, the goal of reliably delivering effective gene-based treatments is now in sight.
ISSN:2327-056X
2327-0578
DOI:10.1146/annurev-virology-101416-041936