NEW TECHNOLOGY FOR SELECTIVE DELIVERY OF PNAS IN CANCER CELLS IN VITRO AND IN VIV


Year of Award:
2007
Award Type:
R21
Project Number:
CA125280
RFA Number:
RFA-CA-07-015
Technology Track:
Molecular & Cellular Analysis Technologies
PI/Project Leader:
ANDREEV, OLEG A
Other PI or Project Leader:
N/A
Institution:
UNIVERSITY OF RHODE ISLAND
Many cancers arise from the gradual accumulation of genetic changes in cells. Gene therapy approaches as well as techniques for recognizing cancer cells with abnormal genes or elevated levels of certain mRNAs include the design and delivery into cancerous cells of antisense and antigene oligonucleotides or their synthetic mimics such as peptide nucleic acids (PNAs). PNAs are highly stable, resistant to nucleases and proteases, and bind RNA and DNA targets in a sequence-specific manner with high affinity. One of the main obstacles for gene therapy is a lack of technology for selective delivery of gene agents into cancer cells in vivo. Here we propose a new technology for selective delivery into cancer cells of PNAs targeting mRNAs involved in tumor growth and metastasis. It is well established that tumors develop a hypoxic and acidic extracellular environment, especially in the earlier stages. We designed a short peptide that is soluble in water and able to insert into the membrane as a transmembrane alpha-helix at low pH (