Specific Promoter Driven Targeting of AAV Vector
The number of clinical trials involving adeno-associated virus (AAV) vectors has increased every year. For continued success, more specific AAV expression cassettes need to be designed to meet the special needs of each disease. Creative Biolabs has accumulated a lot of experience in the design of AAV vector expression cassettes, providing customized design services, improving targeting specificity and increasing gene expression.
Specific Promoter Driven Targeting of AAV Vector
AAV vectors occupy a unique space in drug development. Their structure and genomic complexity present various obstacles in the design and implementation of functional or potency analysis for specific disease targets. The cis-acting elements that regulate transgene expression have the same effect on the success of gene therapy because of the design of vector capsid or envelope. The promoter is a major cis-acting element in the genomic design of AAV vector, which can determine the overall intensity and cell specificity of expression. When the expression is limited to certain cell types in an organ, promoters can be used to mediate cell specificity. For example, in the nervous system, promoters are used to restrict the expression in neurons, astrocytes or oligodendrocytes. Following systemic administration of vectors, cell or tissue specific promoters can be used to limit expression outside the liver.
Figure 1. Cartoon diagram of a generic AAV expression cassette design indicating where modular regulatory elements would be placed. (Powell, 2015)
Development of Specific Promoter Driven Targeting of AAV Vector
Due to the size limitation of AAV's external DNA packaging, the use of cell-specific promoters to improve the targeting specificity of expression boxes needs to be carefully designed. Considering the size limitation, different cis-acting elements are also applied to AAV expression cassettes to enhance cell-specific transgene expression in varying degrees.
Figure 2. Outline of AAV reporter cassettes driven by ubiquitous or photoreceptor promoters. (McDougald, 2019)
At present, in the context of retinal gene transfer, some promoter sequences are involved in the design of AAV vector. Experiments show that this vector has strong safety and effectiveness in the pre-clinical model of hereditary retinal degeneration. In addition, in the hepatic gene transfer of hemophilia B, a single-stranded AAV2 vector was administered via the hepatic artery, carrying human FIX gene expressed under the control of liver-specific promoter, and successfully targeting the liver. It has been proven that it is possible to transform human liver into therapeutic expression with AAV vector.
Features
- Expert team with professional knowledge and project experience can escort your AAV vector related projects;
- Comprehensive and customizable AAV vector design services provide targeted, high expression intensity AAV vectors, which can accelerate the success of your project;
- Faster turnaround time and better after-sales service.
If you are interested in our services, please don't hesitate to contact us and find out about our range of services!
References
- Powell, S.K.; et al. (2015). Viral expression cassette elements to enhance transgene target specificity and expression in gene therapy. Discovery medicine. 19(102): 49.
- McDougald, D.S.; et al. (2019). CRISPR activation enhances in vitro potency of AAV vectors driven by tissue-specific promoters. Molecular Therapy-Methods & Clinical Development. 13: 380-389.
