Small Inhibitory RNAs
The concept of siRNA as a therapeutic modality is still very much in its early days. However, the ability of siRNAs to silence virtually any gene in the genome makes it extremely promising as a potential targeted cancer therapy. LICR is assessing the therapeutic potential of siRNAs with an initial focus on using targeted antibodies to deliver the siRNA molecules.
The siRNA itself is a short double-strand of RNA, the sequence of which is complementary to the DNA sequence of the gene of interest. The siRNA binds to the gene and prevents the expression of the protein the gene encodes. LICR investigators, working with collaborators at the City of Hope (CA, USA), have constructed a series of molecules composed of an siRNA linked to an antibody that targets cancer cells.
The team is now conducting an exhaustive analysis of the effect of different constructs on gene knockdown. This detailed analysis—of the size of the siRNA, the composition of the siRNA, the length of the linker between the siRNA and the antibody, effect of using cleavable and non-cleavable linkers, where and how the linker is attached, and so on—is part of the excruciating, but crucial, minutiae that must be understood in order to fully optimize and assess the potential of a new therapy.
