earticle

영어

Stem cells have significant promise for regenerative medicine, but they first require an understanding of molecular or environmental cues that can regulate their proliferation and differentiation, as well as means to manipulate these signals to control cell behavior. Delivery of genes encoding molecules capable of regulating stem cell function can serve as an effective means to both investigate stem cell biology and to control cell fate for therapeutic applications. Additionally, gene delivery coupled with gene targeting has the potential to introduce mutations, and thereby generate disease models, as well as to correct deleterious genetic mutations in stem cell populations. However, a major obstacle to such applications continues to be the development of efficient and safe gene delivery vectors. Adenoassociated viral (AAV) vectors, which are being broadly explored in clinical trials, have significant promise as therapeutic vectors due to their safety and delivery efficiency, as well as their potential for gene targeting. Unfortunately, no natural AAV variants have been found with optimal properties for infecting stem cells. Due to the significant advantages of the vector, however, engineering AAV vectors to overcome rate limiting steps (i.e., cellular binding, intracellular trafficking, viral unpackaging, etc.) in stem cell transduction may have a high impact for stem cell investigations. Current approaches to design custom AAV vectors are limited to rational peptide insertion into or
chemical modifications of the viral capsid structure. However, since the structure-function relationships of the complex AAV capsids are not fully understood, rationally designing and modifying the AAV capsid to meet specific needs are still challenges. In this presentation, a powerful tool (i.e. directed evolution) to create de novo bio-inspired nanoparticles (i.e., AAV vectors) that can significantly enhance the capabilities of gene delivery as well as gene targeting within stem cells will be introduced, and a variety of potential applications using gene-targeted stem cells will be discussed.