Gene Vectors

gene-vecLocalized gene therapy is an attractive strategy to treat a variety of life-threatening diseases, spanning genetic disorders, infectious diseases and cancers. However, this approach has been largely unsuccessful to date, due to lack of methods to overcome biological and/or immunological barriers. Indeed, it has been said that “there are only three problems in gene therapy – delivery, delivery, and delivery.” (quote from I. M. Verma in Time, 1999; Jan 11). The field of gene therapy is largely divided into two categories, depending on the source of delivery vehicles, namely viral and non-viral gene therapy. Viral vectors, due to their intrinsic capacity to infect cells, are generally more efficient compared to non-viral vectors, but pose safety concerns of insertional mutanegesis and potential oncogenesis. In addition, the efficacy of viral vectors drastically reduces upon repeated dosing, due to their immunogenic properties. Non-viral vectors, despite being relatively less efficient, possess several advantages, including improved safety, reduced immunogenicity, ease of manufacturing and scale up, and the ability to accommodate larger genes compared viral vectors. At the Center for Nanomedicine, we engineer nanoparticle-based synthetic gene vectors that can overcome extra- and intracellular barriers and hence delivering cargo genes to the target cells efficiently. Specifically, we have designed gene vectors capable of penetrating human mucus barriers, vitreous gel in the eyes, and extracellular space in the brain tissues. We have also designed gene vectors capable of overcoming several intracellular barriers, such as cellular membrane and degradative vesicles.

Selected Publications

  • Kim AJ*, Boylan NB*, Suk JS, Hwangbo M, Yu T, Schuster BS, Cebotaru L, Lesniak WG, Oh JS, Adstamongkonkul P, Choi A, Kannan RM, Hanes J. Use of Single-site Functionalized PEG-dendrons to Prepare Gene Vectors that Penetrate Human Mucus Barriers. Angew Chem Int Ed Engl. 52(14):3985-8
  • Boylan NB*, Kim AJ*, Suk JS, Adstamongkonkul P, Lai SK, Zeitlin PL, Hanes J. (2012) Enhancement of Airway Gene Transfer by DNA Nanoparticles Using A pH-Responsive Block Copolymers of Polyethylene glycol and Poly-L-lysine, Biomaterials. 33(7):2361-71.
  • Suk JS, Boylan NJ, Trehan K, Tang BC, Schneider CS, Lin JG, Boyle MP, Zeitlin PL, Lai SK, Cooper MJ, Hanes J. (2011) N-acetylcysteine Enhances Sputum Penetration and Airway Gene Transfer by Highly Compacted DNA Nanoparticles. Mol Ther. 19(11):1981-9.