Gene transfer vector biodistribution: pivotal safety studies in clinical gene therapy development

• Published in: Gene therapy Vol. 11; no. S1; pp. S98 - S108
• Main Authors: Gonin, P, Gaillard, C
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01-10-2004
• Subjects: Adeno-associated virus; Adenovirus; Animals; Biodistribution; DNA - analysis; Expression vectors; Gene Expression; Gene therapy; Genetic Therapy - adverse effects; Genetic Vectors - administration & dosage; Genetic Vectors - metabolism; Humans; Models, Animal; Reverse Transcriptase Polymerase Chain Reaction; Risk assessment; Safety; Tissue Distribution; Toxicity; Transgenes; Vectors (Biology)
• ISSN: 0969-7128; 1476-5462
• DOI: 10.1038/sj.gt.3302378

Techniques allowing for gene transfer vectors biodistribution investigation, in the frame of preclinical gene therapy development, are exposed. Emphasis is given on validation and test performance assessment. In the second part, specific gene vector distribution properties are reviewed (adenovirus, AAV, plasmid, retroviruses, herpes-derived vectors, germline transmission risks). The rationale for biodistribution by quantitative PCR, animal study and result interpretation is discussed. The importance and pivotal role of biodistribution study in gene transfer medicine development is shown through the determination of target organs for toxicity, germline transmission assessment and determination of risks of shedding and spreading of vectors in the gene transfer recipient and the environment.