Light-sensitive polymers for controlled gene silencing

by | Feb 4, 2015

New research describes the use of polymers that can bind siRNAs into nanoscale assemblies that do not disassemble until they are irradiated with UV light.

Small interfering RNAs (siRNAs) are a class of nucleic acids with the potent ability to induce cells to stop producing select cellular building blocks known as proteins.  The specificity in this gene “silencing” is determined by the sequence of the siRNA, and siRNAs can be designed to silence virtually any targeted gene of interest.  Because of this ability to change the expression of specific genes known to control tissue repair and cause a variety of acquired and hereditary diseases, siRNAs are considered highly promising as therapeutics.  However, there are many challenges associated with the delivery of siRNAs to the precise cellular populations, as siRNAs have a short half-life and are not spontaneously internalized by cells.  To overcome these hurdles, various approaches have sought to encapsulate siRNAs within polymer nanoparticles able to protect the siRNAs and improve uptake into target cells.  A key difficulty is that these nanoparticles sometimes fall apart and release siRNA too early, or alternatively, do not fall apart at all.

New research describes the use of novel, positively charged, light-sensitive polymers as materials that can bind negatively charged siRNAs into stable nanoscale assemblies that do not unbind and release siRNA until they are irradiated with UV light.  These materials remain assembled in the presence of common proteins found in blood and various tissues, and they also promote efficient uptake of siRNA into cells. The polymers within these siRNA-containing assemblies react to become negatively charged when irradiated, resulting in the release of siRNA.  When these particles are within cells, siRNA release and gene silencing only occur when the cells are irradiated.  Hence, these materials can be used to control the behavior of specific populations of cells through light, with diverse applications in tissue engineering and other arenas.