Non-Viral Gene Vectors

capsul-100x100Localized 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, and it has been said that “there are only three problems in gene therapy – delivery, delivery, and delivery (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 virus-based (viral) and non-viral gene therapy. Viral vectors, due to their intrinsic capacity to infect cells, are generally more effective compared to non-viral vectors, but pose safety concerns. In addition, the body recognizes viral vectors as being foreign, so the immune system will not allow for more than one treatment. Non-viral vectors, despite being relatively less efficient, possess several advantages: improved safety, easier manufacturing, and the more flexibility with the types of genes that can be delivered. At the Center for Nanomedicine at Wilmer, we engineer nanoparticle-based non-viral gene vectors that can overcome external barriers, such as mucus in the airways and muscle tissue, and hence reach cells to deliver their cargo more effectively. We have designed gene vectors capable of penetrating mucus, vitreous gel in the eyes, and extracellular space in the brain and muscle tissues. We have also designed gene vectors capable of overcoming barriers inside cells, improving upon a major limitation of non-viral gene vectors.

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
  • Mastorakos P, da Silva AL, Chisholm J, Song E, Choi WK, Boyle MP, Morales MM, Hanes J, Suk JS. (2015) Highly compacted biodegradable DNA nanoparticles capable of overcoming the mucus barrier for inhaled lung gene therapy, Proc Natl Acad Sci USA, 112(28):8720-5.
  • Mastorakos P, Zhang C, Berry S, Oh Y, Lee S, Eberhart CG, Woodworth GF, Suk JS, Hanes J. (2015) Highly PEGylated DNA Nanoparticles Provide Uniform and Widespread Gene Transfer in the Brain, Adv Healthc Mater, 4(7):1023-33.