Adeno-Associated Viral Vectors at the Frontier between Tolerance and Immunity

Federico Mingozzi (1, 2) , Hildegard Büning (3, 4, 5)

1 Généthon
2 Thérapie des maladies du muscle strié
3 Department of Internal Medicine
4 CMMC - Center for Molecular Medicine [Cologne]
5 DZIF - German Center for Infection Research - Partner Site Bonn-Cologne

In recent years, the field of in vivo gene transfer with adeno-associated virus (AAV) vectors has seen an extraordinary expansion of applications and investments. Results emerging from clinical trials (1) and the recent market approval of a gene therapy drug for lipoprotein lipase deficiency (2) contributed to the hype around this vector system (3). Indeed, AAV vectors have several features that make them an ideal tool for gene transfer, for example, parental virions are replication deficient and non-pathogenic (4), and vectors can drive expression of a transgene for several years (5, 6) despite the fact that they do not integrate efficiently into the host genome. In recent years, a portfolio of natural AAV isolates (AAV serotypes) differing in tissue tropism has been developed as vectors. This toolbox has been further expanded with engineered AAV capsids developed to enhance efficiency and specificity of gene delivery, and to escape antibody neutralization (7). At the vector genome level, availability of potent promoter/enhancer sequences, codon-optimization of transgenes, and development of self-complementary AAV vectors (8) further enhanced efficacy of gene transfer. Finally, the availability of scalable processes to produce AAV vectors in GMP contributed significantly to the expansion of the field.

Mots clés: AAV vector; immune response; tolerance; vaccine; gene therapy

Domaines: Vaccinologie; Immunologie

Federico Mingozzi, Hildegard Büning. Adeno-Associated Viral Vectors at the Frontier between Tolerance and Immunity. Frontiers in Immunology, 2015, 6, pp.120. ⟨10.3389/fimmu.2015.00120⟩. ⟨hal-01216420⟩