Calando Pharmaceuticals, an siRNA therapeutics company and a majority-owned subsidiary of Arrowhead Research Corporation has announced the publication of a study demonstrating the anti-proliferative effect of the siRNA sequence selected as the therapeutic component of its lead anti-cancer compound, CALAA-01.
The paper, entitled “Potent siRNA Inhibitors of Ribonucleotide Reductase Subunit RRM2 Reduce Cell Proliferation In vitro and In vivo,” was published in the April 1 edition of Clinical Cancer Research, a journal published by the American Association of Cancer Research (AACR).
This paper describes how Calando researchers and their collaborators determined the sequence of siRNA included in Calando’s lead siRNA-containing nanoparticle formulation (CALAA-01).
Numerous putative candidate siRNA duplexes targeting the M2 subunit of ribonucleotide reductase (RRM2) were screened, and those with maximal anti-RRM2 activity were further tested.
The best candidate siRNA duplex demonstrated potent reduction of RRM2 protein levels in cultured cells and achieved a concomitant anti-proliferative effect in cells of multiple species (including human, mouse, rat, and monkey) and cancer types, both in vitro and in vivo. These findings confirm that this duplex is a promising candidate for therapeutic development.
"This paper highlights the results from screening experiments in which the sequence of Calando’s lead anti-RRM2 siRNA was determined,” said Jeremy Heidel, Calando’s Chief Scientific Officer. “This duplex is powerful in its ability to down-regulate its target and elicits a strong anti-proliferative effect in a variety of types of cancer cells."
“These studies demonstrate the potential for this siRNA duplex to have a strong anti-tumor effect,” said John Petrovich, Calando’s Chief Executive Officer.
Petrovich also noted that Calando has filed for patent protection on several siRNA duplexes against RRM2 in a patent application that was published in November 2006 (US Patent Application No. 20060263435) and has licensed patents from Alnylam Pharmaceuticals to enable it to develop and commercialize an RNAi therapeutic against this target.