Although siRNA-based therapeutics have
recently been clinically validated as a strategy to knock down gene expression,
a lesser-known function for short double-stranded RNAs is their ability to turn
on the expression of target genes. Now, an academic team sponsored by MiNA
Therapeutics Ltd. has found a way to attack liver cancer in
rats by using a short activating RNA to upregulate expression of a tumor
suppressor,1 and the company plans to advance the program to the
clinic this year.
The devil is
in the details
researchers contacted by SciBX agreed that upregulating CEBPA
holds promise in HCC, they were concerned by the lack of a clear molecular
explanation for saRNA action.
A clinical formulation
MiNA has now begun clinical testing of a
nanoparticle-based formulation of a CEBPA-upregulating saRNA, MTL-501.
"MTL-501 is in a first-in-human dose-escalation study," said Robert
Habib. MiNA anticipates initiating a Phase I study in the U.K. in under a year.
Donner, A. SciBX 7(5);
Published online Feb. 6, 2014
1. Reebye, V. et al.
Hepatology; published online Dec. 9, 2013; doi:10.1002/hep.26669
Contact: Nagy A. Habib, Imperial College London, London, U.K.
Contact: Vikash Reebye, same affiliation as above
2. McCallister, E. BioCentury
22(3), A1-A5; Jan. 20, 2014
3. Zhou, J. et al. Mol.
Ther. 19, 2228-2238 (2011)
4. Di Ruscio, A. et al.
Nature 503, 371-376 (2013)
Alnylam Pharmaceuticals Inc. (NASDAQ:ALNY), Cambridge, Mass.
Arrowhead Research Corp. (NASDAQ:ARWR), Pasadena, Calif.
Benitec Biopharma Ltd. (ASX:BLT), Balmain, New South Wales, Australia
Biomedical Research Foundation of the Academy of Athens, Athens, Greece
City of Hope,
Dicerna Pharmaceuticals Inc. (NASDAQ:DRNA), Watertown, Mass.
General University Hospital of Larissa, Larissa, Greece
Genzyme Corp., Cambridge, Mass.
Harvard Medical School, Boston, Mass.
High Technology Medical Center, Tbilisi, Georgia
Imperial College London, London, U.K.
Marseille Interdisciplinary Center for Nanoscience, Marseille, France
MiNA Therapeutics Ltd., London, U.K.
National Taiwan University, Taipei City, Taiwan
Norwegian University of Science and Technology, Trondheim, Norway
Opko Health Inc. (NYSE:OPK; Tel Aviv:OPK), Miami, Fla.
Qatar Biomedical Research Institute, Doha, Qatar
RaNA Therapeutics Inc., Cambridge, Mass.
Sanofi (Euronext:SAN; NYSE:SNY), Paris, France
Tbilisi State Medical University, Tbilisi, Georgia
University of California, Los Angeles, Calif.
University of Miami Miller School of Medicine, Miami, Fla.
University of Pennsylvania, Philadelphia, Pa.