New Research Published on Impact of Targeting on Biodistribution and Efficacy of siRNA Using Calando Pharmaceuticals siRNA Delivery Technology
News Sep 26, 2007
Calando Pharmaceuticals has announced the publication of a study in the Proceedings of the National Academy of Sciences (PNAS) the scientific journal of the NAS.
Dr. Mark Davis, professor of chemical engineering at Caltech, and his colleagues at UCLA used Calando's proprietary RONDEL™ polymer technology for delivering siRNA in mice.
Dr. Davis is a founder and Chief Scientific Advisor to Calando.
The paper, entitled "Impact of tumor-specific targeting on the biodistribution and efficacy of siRNA nanoparticles measured by multimodality in vivo imaging", was published online in the Early Edition of the PNAS on September 17, 2007.
In the study, Dr. Davis and his colleagues used positron-emission tomography (PET) and bioluminescent imaging (BLI) to quantify biodistribution and function in mice of siRNA nanoparticles formulated with Calando's proprietary RONDEL™ polymer technology for delivering siRNA and other nucleic acids.
Some were targeted with transferrin, an iron-carrying protein, and others were not. While all the particles - targeted and not - accumulated to a similar extent in tumors, the targeted particles reduced the BLI signal from tumor cells by 50% relative to the non-targeted particles.
These results show that the advantages of targeted nanoparticles appear to be associated with uptake into tumor cells, and not to overall tumor localization.
"This work reveals that the primary advantage of targeted nanoparticles for tumor-specific delivery of siRNA is the enhanced uptake in tumor cells rather than altered biodistribution," said Mark Davis.
"The conclusions should be applicable to nanoparticle delivery systems in general, and they emphasize why targeted particles should show greater efficacy than non-targeted particles."
"This study demonstrates the importance of including a targeting ligand for achieving efficacy in tumor cell gene inhibition with siRNA," said John Petrovich, President and CEO of Calando Pharmaceuticals.
"Calando plans to file an investigational new drug (IND) application with the US Food and Drug Administration for a Phase I clinical trial in cancer with what we believe will be the first targeted, systemically-delivered siRNA, using a similar formulation carrying siRNA RRM2, a protein essential to cell replication in tumors".