The National Institutes of Health announced last week that it has earmarked roughly $5.6 million to fund between 13 and 17 new grants in 2006 focused on improving technologies associated with the uptake, stability, processing, and delivery of tissue- and cell-specific RNAi compounds.
The NIH said it is accepting grant proposals both from for-profit and non-profit organizations, including universities, hospitals, laboratories, and units of state or local government. The grants are open to US-based institutions only.
The cash is aimed at helping researchers better understand the uptake and processing of RNAi compounds by target tissues; assess stability, half-life, and off-target effects of these agents in target tissues; and determine optimal delivery methods for RNAi molecule uptake by the target tissues.
"While RNAi inhibits the expression of genes in a sequence-specific manner, issues of specificity and processing are not yet clear," the NIH stated in a request for grant applications.
"While RNAi inhibits the expression of genes in a sequence-specific manner, issues of specificity and processing are not yet clear." The grant is also "intended to support the development of novel and highly efficient delivery methodologies."
"The potential of RNAi as a therapeutic tool is due to the ubiquitous presence of the enzymatic machinery necessary to process microRNA … [but] since this machinery is predominantly used in mammalian cells for microRNA mediated gene regulation, the use of siRNA might produce differential effects during interaction with the silencing complexes," the agency noted. "These effects may differ across tissues, as well. Uptake, stability, and processing may differ among various tissues and this [call for applications] focuses on addressing these issues specifically relevant to the mission of the participating [NIH] institutes.
"The off-target effects and toxicities of RNAi [compounds] in [various] tissues need to be understood to fully realize the therapeutic potential of RNA interference," the NIH added. Furthermore, delivery to target tissues has proven to be a major barrier to the development of RNAi drugs.
Though a number of strategies have been developed to deliver siRNAs, "effective approaches to in vivo delivery to most target organs are lacking," the NIH said. "This [funding opportunity] is also intended to support the development of novel and highly efficient delivery methodologies."
The following NIH institutes are participating in the funding opportunity:
- The National Heart, Lung, and Blood Institute intends to commit approximately $1.5 million to support between four and five grant projects. The NIH said that this institute is particularly interested in research focusing on the cardiovascular system, the pulmonary system, and sleep-regulating systems.
- The National Institute of Neurological Diseases and Stroke has committed about $1.5 million to fund between four and five projects. This institute is interested in RNAi targeting nervous system cells and tissues, neurological diseases such as HIV-dementia, and overcoming difficulties in delivering RNAi agents across the blood-brain barrier. Additionally, using RNAi to manipulate the permeability of endothelial cells in the brain microvasculature, and their interactions with brain cells of the neurovascular unit, is of particular interest to the NINDS, the NIH noted.
- The National Institute of Allergy and Infectious Diseases has set aside $1 million to support two or three programs. This institute, the NIH said, is seeking grant proposals the focus on the use of RNAi to regulate host-pathogen interactions. Specifically, grant applications should focus on the innate immune system or NIAID category A-C pathogens, such as the bacterium that causes anthrax; arenaviruses; flaviruses; influenza viruses; rabies viruses; and the virus known to cause severe acute respiratory syndrome.
- The National Institute of Diabetes and Digestive and Kidney Diseases has committed $400,000 to fund one grant project. This institute, said the NIH, is interested in proposals dealing with cell types associated with the endocrine, hepatic, nephrological, gastrointestinal, urological, and hematological systems. This may include projects investigating insulin resistance, obesity, and autoimmune diseases.
- The National Institute of Arthritis and Musculoskeletal and Skin Diseases has also committed $400,000 to support one project. Of particular interest to this institute, the NIH said, are gene-silencing approaches to treating disease and injuries affecting muscle, bone, joints, connective tissue, and skin.
- The National Institute of General Medical Sciences has set aside $400,000 to fund one research proposal addressing the basic mechanisms of RNAi stability, delivery, and uptake by cells, the NIH said.
- The National Institute of Dental and Cranofacial Research intends to commit $400,000 to support one grant project focused on oral, dental, and craniofacial tissues, including the treatment and repair of these tissues.
The NIH hopes the grants will help researchers to determine stability and half-life of RNAi agents, and their potential toxicity in cells and tissues; elucidate of RNAi delivery and uptake processes in target tissues and cells; develop chemical modifications that allow or regulate distribution, or chemical modifications that will minimize off-target effects; determine off-target effects in target tissues and cells; and identify chemical modifications that enhance the pharmacokinetics of siRNAs, among other goals.
Letters of intent are due to the various NIH institutes by Dec. 21, 2005. Applications must be submitted by Jan. 18, 2006. The various NIH agencies will review the applications between June and September, 2006, with the end of September being the earlier anticipated start date for grant projects.
Specific details about the funding opportunity, as well as information on NIH institute contacts and application instructions, can be found at http://grants.nih.gov/grants/guide/rfa-files/RFA-HL-05-019.html.
Doug Macron ([email protected])