Groove Biopharma focuses on the generation of novel microRNA (miRNA)-targeted therapeutics with improved properties, such as higher potency and enhanced pharmacodynamic activity. Endogenous microRNAs (miRNAs) are involved in extensive regulatory networks for many target genes and pathways. Groove’s core technology addresses a new avenue of nucleotide therapeutic drug discovery via modulation of cellular miRNA. Using exclusively licensed technology, Groove Biopharma is generating a series of lead candidates with the potential to be best-in-class programs. By incorporating proprietary structural modifications into miRNA therapeutics, the Groove technology platform presents promising potential for treating a wide range of diseases, including cancer, fibrosis, and infectious disease.
Founded in 2008 based on proprietary technology licensed from Nanogen, a publically-traded company recently acquired by Elitech Group. microRNA discovery platform that harnesses Minor Groove Binder (MGB) technology for the enhancement of potency and the improvement of drug properties of miRNA targeted therapeutics.
Lead nucleotide therapeutic programs against known and novel targets developed in an active sequence discovery effort.
Funded and managed by Accelerator Corporation based in Seattle, WA.
David Crowe, Ph.D., Senior Director of Research. Previously VP, Research at Recodogen Corp. and Senior Scientist and Program Leader at ICOS Corp.
Board of Directors
- Carl Weissman, Chairman & CEO, Accelerator Corporation
- Steven Gillis, Ph.D., Managing Director, ARCH Venture Partners
- Chad Waite, Managing Director, OVP Venture Partners
- Thong Le, Managing Director, WRF Capital
- Brian Atwood, Managing Director, Versant Ventures
- Merl Hoekstra, Group Vice-President, Elitech Group
MicroRNA (miRNA) is a newly discovered post-transcriptional regulator of gene expression. miRNAs are ~22 nucleotide long, single-stranded RNAs that guide an RNA/protein complex to recognition sequences in target messenger RNA (mRNA) transcripts. This interaction results in silencing or attenuation of gene expression by triggering the degradation of the target mRNA or inhibiting its translation. A single miRNA can target multiple mRNA transcripts, providing a cellular mechanism whereby a single regulatory factor can modulate the expression of a suite of genes. Groove Biopharma’s miRNA antagonists specifically block the ability of miRs to silence target mRNAs, resulting in selective protein expression.
Some miRs have been shown to be differentially expressed in a tissue-specific manner, and are part of the host response to viral infection and chronic injury. Aberrant miRNA expression can also contribute to cellular transformation and metastasis. Aberrant miRNA expression is associated with numerous disease states, providing an opportunity for novel therapeutic intervention. Since a single miRNA can regulate several mRNAs within a biological pathway, this provides the opportunity to regulate the levels of multiple proteins associated with disease at one time. Alteration of miRNA function in this manner can alter whole animal physiology and therapeutics which target miRs represent an entirely new approach to drug development.
To date, most miRNA therapeutics are limited by the same difficulties shared by conventional therapeutics in addition to some that are specific to oligonucleotide based therapeutics. Historically, oligonucleotide therapeutics have been plagued by low potency, high toxicity and the need for complex delivery systems. Groove Biopharma’s proprietary technology increases potency, reducing the risk of toxicity, while serving as its own delivery vehicle. Groove’s technology greatly increases distribution to a variety of tissues, opening the door to a greater number of disease indications. These observations have been reproduced in a variety of model systems and using a variety of quantitative and functional readouts.
Groove Biopharma’s proprietary platform technology is based on use of Minor Groove Binding agents (MGB) best known for their use in the TaqMan® assay. MGB technology represents a well-established modification that substantially enhances oligonucleotide properties without an apparent loss of selectivity. Grove has investigated many structural parameters of the MGB-oligonucleotide conjugate, including MGB composition, orientation, and linker length, providing a variety of options to fine tune target specificity, potency, and physical/chemical properties.
Groove Biopharma’s MGB Technology intellectual property estate is highly developed and licensed exclusively to Groove. Groove is developing technology to simultaneously target multiple components in signaling pathways associated with the pathogenesis and etiology of disease. Lead therapeutic programs aim to inhibit or augment microRNA targets through the use of oligonucleotide mimetics in several indications, including cancer, fibrosis, and infectious disease. Groove Biopharma has executed, and continues to execute, preclinical studies to verify that Groove's proprietary technology can fundamentally improve upon the current approaches to the treatment of human disease.