Thursday, February 6, 2014
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activating RNAs (saRNAs) to enhance CCAAT
enhancer binding protein-a (CEBPA)-dependent
gene expression in liver cancer
Cell culture and rat
studies suggest dendrimer-formulated saRNAs that bind target gene promoters
could help treat cancer. CEPBA-saRNA was conjugated to a triethanolamine core
poly(amidoamine) dendrimer for in vivo delivery. In a liver cancer
cell line, CEBPA-saRNA increased secretion of albumin and decreased cell
proliferation compared with a scrambled saRNA while maintaining hepatocyte
function. In a cirrhotic rat model with associated liver cancer, a
CEBPA-saRNA dendrimer conjugate increased levels of serum albumin and
decreased tumor burden compared with saline or scrambled saRNA-dendrimer,
suggesting improved liver function and antitumor activity. Next steps include
developing an saRNA-nanoparticle candidate for clinical trials (see RNA is for activation,
Published online Feb. 6, 2014
Patents filed; available
for licensing from MiNA
Contact: Robert Habib, MiNA
Therapeutics Ltd., London, U.K.
Reebye, V. et al.
Hepatology; published online Dec. 9, 2013;
Contact: Nagy A. Habib, Imperial College London, London, U.K.
Contact: Vikash Reebye, same affiliation as above
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