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IDENTIFICATION OF AN INHIBITOR OF MICRORNA-122 IN LIVER

Award Number: R43AI072802
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/01/2007
PERIOD OF PERFORMANCE END DATE: 01/31/2009

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IDENTIFICATION OF AN INHIBITOR OF MICRORNA-122 IN LIVER - DESCRIPTION (provided by applicant): MicroRNAs (miRs) are 21-23 nucleotide endogenously expressed RNAs. One of these, miR-122, is highly and specifically expressed in adult liver. A recent report by Jopling et al (Science 309, 1577-1581, 2005) demonstrates a role for miR-122 in replication of hepatitis C virus (HCV) RNA in human cells. Two other reports (Krutzfeldt et al, Nature 438, 685-689, 2005; Esau et al, Cell Metab, 3, 87-89, 2006) demonstrated inhibition of miR-122 in mouse liver using chemically modified antisense oligonucleotides (ASOs). In this application we propose to prepare and test chemically modified ASOs for inhibition of miR-122 in mouse hepatocytes, mouse liver and in a cellular assay for HCV replication. The ultimate goal of this research is development of an anti-miR-122 ASO therapeutic for treatment of HCV. Hepatitis C virus (HCV) infection can progress to significant liver disease; current treatments are often ineffective. We propose to identify a novel therapeutic to treat HCV in humans. A novel therapeutic offers the potential of reducing the severe and growing public health burden of HCV. MicroRNA biology is in its infancy and therapeutic applications for modulators of miRs are likely to be identified in the future. Because we are targeting a microRNA, we will also gain insight into the biological roles of microRNA and into methods for inhibition of miR activity. A long term benefit of this research will be application of what is learned in this study to development of anti-miR therapeutics for other indications.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2008 ( Subtotal = $132,885 )
2008	2008	ISIS PHARMACEUTICALS	2292 FARADAY AVE	CARLSBAD	CA	92008	SAN DIEGO	USA	Microbiology and Infectious Diseases Research	000	2	9/4/2008	NON-COMPETING CONTINUATION	$132,885
														Subtotal = $132,885

Issue Date FY: 2007 ( Subtotal = $299,390 )
2007	2007	ISIS PHARMACEUTICALS	2292 FARADAY AVE	CARLSBAD	CA	92008	SAN DIEGO	USA	Microbiology and Infectious Diseases Research	000	1	7/30/2007	NEW	$299,390
														Subtotal = $299,390

Grand Total All Awards = $432,275

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IDENTIFICATION OF AN INHIBITOR OF MICRORNA-122 IN LIVER

Award Number: R43AI072802

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 08/01/2007

PERIOD OF PERFORMANCE END DATE: 01/31/2009

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