Tissue/Cell Specific Targeting Advanced Adeno-Associated Virus Vector Service
The development of tissue/cell specific targeting advanced adeno-associated virus (AAV) vector enables better, more effective and specific viral vectors to be better used in gene therapy. With the continuous understanding of the structure-function relationship of AAV, improved library generation and innovative screening methods, we can develop more suitable AAV vectors for the treatment of specific diseases. Whatever the stage of your research, scientists at Creative Biolabs will work with you to provide customized AAV services that best meet your needs.
Introduction of Targeting Advanced AAV Vector
One of the obstacles in gene therapy is the requirement to optimize the gene delivery system, that is, to achieve efficient and selective genetically modified production in specific cells or tissues. Exploiting native vector tropism can sometimes achieve this goal without additional modifications. For example, adenovirus infection in hepatocytes or AAV infection in intramuscular skeletal muscles after systemic administration may allow high-level, site-selective gene production. However, in some diseases, it is difficult for target cell populations to be transduced in vivo through available carrier systems. Typical examples include cancer and various cardiovascular diseases. Therefore, it is necessary to continuously modify the vector in order to improve its targeting.
Tissue/Cell Specific Targeting AAV Vector Service
Targeting can be achieved at the vector level: cell interaction (transductional targeting) and transgene regulation (transcriptional targeting). Of course, the connection between vectors and cell surface is the main mechanism determining vector tropism, so it is the initial focus of redesigning new tropism, which can improve the efficiency of gene transfer or introduce selectivity or both, depending on downstream applications. At present, we can provide the following two aspects of vector engineering design services.
AAV Capsid Modification
Various methods of vector capsid engineering have shown promise in vitro, including indirect targeting through ligation subsystems and direct targeting through the insertion of antibody or receptor-specific small peptide motifs. Other strategies, including the creation of mosaic or chimeric capsids and directed evolution, have also been used to successfully reposition AAV vectors. The reasonable design depends on a thorough understanding of the structure-function relationship among the major amino acid sequences, the assembled fourth-order structures and the biological phenotypes of AAV capsids. We have successfully applied the educated capsid design, changed the specific targeting of tissue, avoided immune recognition, and improved the post-processing of the approach.
Figure 1. Rational design strategies for AAV capsid engineering. (Lee, 2018)
Transcriptional Adjusting
Due to the highly diversified application of vectors and target pathological list, transductional targeting remains a major technical challenge. In the case of viral vectors, a detailed understanding of the structure and function of the capsid and the availability of appropriate targeting agents are needed. At present, we have successfully constructed two strategies for AAV transductional adjusting, which are specific promoter-driven targeting and hypoxia regulatory element targeting, showing good results in gene therapy.
Figure 2. Transductional targeting of AAV serotype 2 (AAV-2). (Baker, 2003)
Creative Biolabs provides a wide range of customized AAV vector design services at a reasonable cost and fast turnaround time. Our experienced scientists are ready for difficult projects. Please feel free to contact us for details of your projects.
References
- Lee, E.J.; et al. (2018). Adeno-associated virus (AAV) vectors: rational design strategies for capsid engineering. Current opinion in biomedical engineering. 7: 58-63.
- Baker, A.H. (2003). Targeting AAV vectors. Molecular Therapy. 7(4): 433-434.
