Gene transfer vectors are widely used in preclinical studies in disease animal models and as research tools to achieve gene transfer in vitro and in vivo. There is no single vector that is adequate for all applications, and the gene transfer vector has to be carefully chosen depending on disease, targeted cell type, number of treatments required, and the size and nature of the gene to be delivered.
Viral vectors were the first to be developed, as they exploit the natural property of viruses to transfer their genetic material into the nucleus of infected cells. Vectors derived from DNA viruses do not usually integrate into the host genome and are not replicated at cell division. Therefore, long-term transgene expression from DNA virus-derived vectors is restricted to post-mitotic cells.
Our Vector Core is devoted to providing research grade adeno-associated viral (AAV) vector and adenoviral (Ad) vectors to TIGEM researchers at low cost with a short turn-around time.
Vectors derived from AAV are attractive for in vivo gene transfer because of its favorable safety profile and long-term transgene expression generally observed following a single AAV administration by multiple routes. AAV vectors have been successfully used in clinical trials targeting the liver, muscle, retina and central nervous system.
The strength behind the AAV vector design lies in the fact that the capsid proteins may be exchanged between different AAV serotypes and that AAV vectors with different capsids target specific cell types in vivo. The packaging capacity of AAV is about 4.5 Kb.
Ad-derived vectors are excellent gene transfer vectors due to their ability to efficiently infect a variety of quiescent and proliferating cell types from various species and produce high-level transgene expression.
First generation adenoviral (FGAd) vectors have foreign DNA inserted in place of early region 1 (E1) and are replication defective. In vivo administration of FGAd results in toxicity and transient transgene expression, and thus helper-dependent adenoviral vectors are more suitable for in vivo studies requiring long-term expression. Nevertheless, these vectors remain very useful to achieve efficient transgene expression in a wide variety of cell types.
Helper-dependent adenoviral (HDAd) are deleted of all viral coding sequences and are superior to FGAd in terms of safety and efficacy. HDAd vectors have a large cloning capacity of up to ~37 kb. In several preclinical studies, HDAd vectors have shown long-term, and in some cases, even life-long phenotypic correction without chronic toxicity.