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Platform Delivery Technologies for Nucleic Acid Therapeutics (R41/R42)



There are thousands of rare diseases, and a substantial fraction of these are monogenic disorders, resulting from mutations in a single gene. For such diseases, nucleic acid therapeutics are of potentially broad therapeutic potential. It is important to note, however, that the therapeutic potential of nucleic acids is not limited to rare monogenetic diseases, but also includes more common conditions such as infectious diseases, cancer, and addictive disorders.

Examples of nucleic acid therapeutics include but are not limited to: small interfering RNA (siRNA), microRNA (miRNA), microRNA antagonists (antagomiRs), aptamers, messenger RNA (mRNA), splice-switching oligonucleotides, antisense oligonucleotides, plasmids, minicircles,  or other circular DNAs encoding messenger RNAs and transcription regulatory sequences (e.g. closed-ended, linear duplexes).

Despite the broad and expanding therapeutic potential of nucleic acids, a major limiting factor remains the ability to deliver these molecules into affected cells and tissues. This limitation is due to the fact that, compared to small molecule drugs, nucleic acids are relatively large, negatively charged polymers, which presents significant challenges from the standpoint of drug delivery. These, as well as, other factors have to date limited the utility of nucleic acids as therapeutics.

While some recent progress has been made towards the delivery of certain types of nucleic acids into some tissues, such as the liver, there is a compelling need for the development of novel delivery vehicles for different tissues and cell types.

Research Objectives

The purpose of this Funding Opportunity Announcement (FOA) is to stimulate small businesses to develop platform technologies for the delivery of nucleic acids into specific cells and tissues. For the purposes of this FOA, platform technologies are those that are able to deliver nucleic acids to tissues in a sequence-independent manner, and as such are in principle applicable to the treatment of multiple diseases. Applications to develop technologies that co-deliver nucleic acids along with other therapeutics (e.g. proteins, lipids, small molecule drugs) are also encouraged to apply to the FOA.

This initiative will support small business development of nucleic acid delivery vehicles including (but not limited to) those listed below, alone or in combination.

  • Exosomes; small vesicles that are secreted by cells into which nucleic acids can be incorporated for delivery.
  • Nanoparticles/Liposomes, which may be targeted to specific organs or cell types by the inclusion of a targeting molecule;
  • Viral vectors;
  • Condensates: molecules that condense nucleic acids into a physical state that can enter cells
  • Carriers: compounds that interact with nucleic acids, via either covalent or non-covalent interaction, and thereby facilitating nucleic acid uptake into cells.
  • Chemical modification of nucleic acids that facilitate delivery into cells.
  • Devices that can transfer nucleic acids into cells and tissue by physical means.

In contrast to many other NIH Institutes and Centers, NCATS does not focus on specific diseases, but rather on broader challenges and roadblock to translation that are relevant to all diseases. While we expect that applications will focus on a specific “use case” disease to demonstrate the nucleic acid delivery technology, key criteria for evaluating applications will be the capacity for use in multiple diseases. This capacity should be clearly addressed in the application, as well as justification for the chosen use case.

NCATS will give priority to technologies relevant to the treatment of diseases other than cancer.

Applications that focus on using nucleic acid technologies to treat infectious, immunologic and allergic diseases will be assigned to NIAID. SBIR Research Topic document:

Applications for technologies to deliver nucleic acids into cells ex vivo (i.e. in tissue culture) or for research purposes will not be supported by this Funding Announcement.   


See Section VIII. Other Information for award authorities and regulations.

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