434083 Engineering Delivery Vehicles for siRNA Therapeutics

Thursday, November 12, 2015: 1:42 PM
251A (Salt Palace Convention Center)
Daniel Vocelle, Michigan State University, EAST LANSING, MI, Olivia Chesniak, Chemistry, Michigan State University, East Lansing, MI, Mitch Smith, Michigan State University, East Lansing, MI, Christina Chan, Chemical Engineering and Materials Science and Materials Science, Michigan State University, East Lansing, MI and S. Patrick Walton, Chemical Engineering and Materials Science, Michigan State University, East Lansing, MI

New therapeutic approaches are needed given that small molecule and protein-based drugs are unable to treat 85% of known disease-associated proteins. One potential candidate, short interfering RNA (siRNA) therapeutics, is capable of highly specific targeting for a wide range of proteins through the use of RNA interference (RNAi). siRNA therapeutics have been developed for cancers, genetic disorders, and infectious diseases but are currently limited by delivery vehicles that are toxic, immunogenic, or ineffective. While many types of delivery vehicles have been developed, there is little consensus regarding the mechanisms or characteristics that determine which delivery vehicles will succeed.

Our goal is to define nanoparticle characteristics that are essential for siRNA delivery. Using silica nanoparticles (SNPs), we are investigating delivery criteria among four main categories: sequence specific mRNA degradation (silencing), siRNA binding affinity, membrane translocation, and intracellular trafficking. Using SNPs, vehicle size, structure, charge, and surface functionalization can be varied to determine optimal vehicle design criteria.

The presentation will describe our results to date demonstrating that multiple characteristics influence the siRNA silencing that can be achieved, including amine content, stability of the SNPs at low pH, the quantity of siRNA bound per SNP, and the presence of carbohydrates (i.e., dextran).

Extended Abstract: File Not Uploaded
See more of this Session: Biomaterials for Nucleic Acid Delivery
See more of this Group/Topical: Materials Engineering and Sciences Division