Synthesis of New Polyamines for siRNA Complexation and Delivery
(2010 - Present)
Investigator:
Mindy Levine, University of Rhode Island Mentor:
James Manley, Columbia University
Abstract: The use of siRNA for
the treatment of various diseases, including cancer and ocular ailments,
is a remarkably promising area of research, although new and more
efficient delivery methods are still needed. Proposed herein is the
development of a new class of chiral polyamines for siRNA complexation
and delivery. These polyamines contain several features that are
expected to lead to high binding affinities with siRNA, including
cationic amines, hydrophobic side chains, and well-defined
three-dimensional configurations dictated by the chiral side chains.
Moreover, the polyamines contain fluorescent substituents that will
allow for the direct imaging of the siRNA-polyamine complexes in
cellular environments. The complexation of the polyamines with a model
siRNA will be measured using a variety of analytical techniques, and the
success of the polyamines in complexing and delivering siRNA will be
measured using an in vivo assay with mouse NIH 3T3 cells. The successful
transfection of siRNA using these notoriously difficult to transfect
cells will demonstrate the advantages of these new polyamines for siRNA
complexation and delivery.
The siRNA that will be transfected is one targeted against
hnRNPA1 expression, which is an RNA-protein complex involved in PKM gene
regulation. Aberrant expression of hnRNPA1 has been implicated in a
variety of cancers. As such, targeting hnRNPA1 using siRNA will enable the
development of new and effective disease treatments.
