LOR-1284
RNA interference (RNAi) is an exciting targeted technology for the silencing of disease-causing genes with double stranded RNA molecules known as short interfering RNA (siRNA). A key advantage of siRNA technology is that it can inhibit drug targets that are difficult to block using other technologies. There is tremendous interest in siRNA-based therapeutics, and pharmaceutical companies and biotechs worldwide are developing siRNA for a range of diseases, including viral diseases, age-related macular degeneration and cancer.
Lorus recognized the potential of RNAi early on and has developed an siRNA program targeting the R2 subunit of ribonucleotide reductase for cancer therapy building on its established expertise in RNA/DNA therapeutics. R2 is a well-validated target that is highly overexpressed in cancer cells and cooperates with a variety of cancer-causing oncogenes to enhance cancer progression. Targeted knockdown of R2 mRNA and protein expression correlates with antitumor activity.
Lorus’ lead siRNA, LOR-1284 (formerly known as siRNA-1284), is currently in preclinical development, and has demonstrated strong antitumor activity in several human tumor models including renal cell carcinoma, melanoma and colon adenocarcinoma.
Lorus is conducting further preclinical studies to determine the range of antitumor efficacy for LOR-1284, together with studies on mechanism of action, nonclinical toxicity, and dose optimization in order to advance LOR-1284 into clinical trials in cancer indications.
Lorus is currently collaborating with partners developing siRNA delivery technologies for targeting specific cancers in order to enhance the potential of this therapeutic approach. One such partner is the Ohio State University (OSU) with whom Lorus has had a long-standing collaboration to study the impact of OSU’s nanoparticle delivery on enhancing the efficacy of the “naked” LOR-1284 siRNA. Earlier studies at OSU have shown that nanoparticle delivery systems can be applied to siRNAs such as LOR-1284, and that the resulting nanoparticles were highly biologically active in down regulation of target genes.
In March 2009, OSU’s investigators received a $2M grant from the National Institute of Health (NIH) to develop its liposomal nano-delivery technology in cooperation with Lorus for LOR-1284. The grant will allow OSU to complete the preclinical program, which includes determining the range of antitumor efficacy, mechanism of action, nonclinical toxicity, and dose optimization in order to advance the LOR-1284 nanotherapeutic into clinical trials in cancer indications.