Regulus Therapeutics Inc. today announced that new pre-clinical data
from multiple therapeutic programs were presented at the “RNA Silencing:
Mechanism, Biology and Application” Keystone Symposium held January 14 –
19, 2010 in Keystone, Colorado. Regulus and its collaborators presented
data showing microRNA target regulation by anti-miRs, as well as data
from therapeutic programs focused on oncology, immune disease and
hepatitis C virus (HCV) infection.
“The field of microRNA discovery and therapeutic development is growing
exponentially and at a tipping point”
“The field of microRNA discovery and therapeutic development is growing
exponentially and at a tipping point,” said Peter S. Linsley, Ph.D.,
chief scientific officer of Regulus. “The company’s innovative
chemistries and unique understanding behind the biology of diseases
caused by microRNA dysregulation positions Regulus to lead the
development of a new class of high-impact medicines based on microRNA.”
Oncology
In a poster titled “microRNA mimics as cancer therapeutics,” Regulus
scientists presented in vivo data demonstrating delivery of miR
mimics and microRNA target repression in an orthotopic liver tumor mouse
model. Using lipid nanoparticles developed by collaborators at Alnylam
Pharmaceuticals, Regulus scientists demonstrated effective delivery of a
miR-34a mimic to both the normal liver cells and human hepatocellular
carcinoma cells growing as tumors within the liver. Microarray profiling
of the livers from mice treated with the miR-34a mimic displayed a
significant down-regulation of messenger RNA targets of miR-34a. Within
the tumors, Regulus scientists saw a similar down-regulation of
messenger RNA targets. When Regulus scientists further analyzed the
down-regulated messenger RNAs for functional significance, it was
discovered that several cell cycle progression and cellular division
genes were over represented. This demonstrates the potential utility of
a miR-34a mimic delivered by lipid nanoparticles for the treatment of
liver cancer.
anti-miR target regulation in immune cells
Regulus, in an alliance with GlaxoSmithKline, presented data from
immuno-inflammatory disorders program in a poster titled “Inhibition of
microRNA function in macrophages by anti-miRs”. The study provided the
initial demonstration of a pharmacological effect in immune cells by
specific microRNA inhibition. The study showed that systemically
delivered anti-miRs distribute to immune cells and show functional
target regulation, as measured by a statistically significant
de-repression of seed-matched messenger RNA transcripts. Characterizing
microRNA targets using this approach is uncovering the role that
microRNAs play in cells of the immune system, and opening the door for
microRNA therapies in immuno-inflammatory diseases.
Autoimmunity and Cancer