Bio-reducible polymers for gene delivery with high transfection efficiency and low cytotoxicity.

Both viral and non-viral delivery systems have been used for gene therapy, but non-viral vectors present a variety of advantages, including scalability, low immune response, flexible loading capacity, and stability. Widespread adoption of non-viral gene vectors, however, has been limited by toxicity and transfection efficiency concerns.

Multiple polymers for more efficient delivery of genetic material have been developed. The first is a novel arginine-conjugating bioreducible poly(amido amine) polymer that can degrade into nontoxic molecules in an intracellular environment. Mixing the polymer with PEG inhibits plasmid DNA condensation, improves biocompatibility, and enables in vivo applications. The second polymer is a poly(ethylamine) (PEI)-based gene delivery system, made through polymerization of cysteine and dendrimer branches. The polymer has a smaller molecular weight, which increases the stability of the complex and lowers cytotoxicity. Conjugating PEI to poly(cystaminebis(acrylamide)- diaminohexane) (poly(CBA-DAH)) via a disulfide bond further decreases toxicity and allows genetic material to be released easily.

Design & Development

• Facilitates delivery of genetic materials such as pDNA, siRNA, and pshRNA.
• Improves transfection efficiency (up to 10x that of Lipofectamine).
• Reduces toxicity.
• Improves gene silencing efficiency.
• Enables additional in vivo applications through increased biocompatibility.

Kim, Tae-Il, and Sung Wan Kim. “Bioreducible polymers for gene delivery.” Reactive & functional polymers vol. 71,3 (2011): 344-349. doi:10.1016/j.reactfunctpolym.2010.11.016

Publication Number: US-2010-0010067-A1
Patent Title: Arginine-Conjugated Bioreducible Poly(disulfide amine) Polymers for Gene Delivery System
Jurisdiction/Country: United States
Application Type: Non-Provisional

Aaron Duffy
(801) 585-1377
aaron.duffy@utah.edu