RNA interference (RNAi) and Gene Therapy

RNA interference (RNAi) and Gene Therapy

RNAi is a mechanism whereby relatively short (~22bp) RNAs can inhibit or “knock down” the expression of specific genes in cells. Considerable progress has been made in the application of inhibitory RNAs to the treatment of diseases. Small inhibitory (si), double stranded RNAs can be synthesized to inhibit the translation of specific genes. We have extensive experience in the preparation and utilization of siRNAs to suppress the expression of various genes involved in a wide range of pathological processes including cancer and infectious diseases. Because RNA is highly susceptible to enzymatic degradation in vivo, we have developed a range of nanoparticle packaging systems to protect siRNA when delivered as therapeutic nanocomplexes to knock down the expression of specific genes. The specificity of this system can be further enhanced by adding ligands, including monoclonal antibodies, to target the delivery of therapeutic nanocomplexes to specific cells, tissues, and organs (see Targeted Drug Delivery). We can also add imaging agents to therapeutic nanocomplexes providing the capacity to simultaneously “see and treat”, the basis of the new field of theranostics.

 

Applications

We have used this technology for the treatment of metastatic cancers by systemically administering in vivo nanocomplexes containing antiangiogenic siRNAs targeted to tumor specific antigens. This approach is effective in delivering therapeutic nanocomplexes to treat tumors and infections of the central nervous system.

 

  • Custom synthesis of siRNAs to knock down the expression of specific genes in vitro and in vivo.
  • Encapsulation of siRNA within biocompatible and biodegradable nanoparticles capable of the
  • Formulation of therapeutic nanocomplexes capable of the controlled, timed release of their payloads (minutes, hours, days, weeks).
  • Addition of imaging agents to therapeutic nanocomplexes to simultaneously “see and treat” for theranostic applications.