HHS SBIR PA-14-307

The purpose of this initiative is to incentivize small businesses to generate new technologies and products for  delivering nucleic acids  into cells and tissues for the purpose of treatment or prevention of human disease. 

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.  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, and plasmid or other circular DNAs encoding messenger RNAs and transcription regulatory sequences.

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. 

Despite the broad therapeutic potential of nucleic acids, the major limiting factor is 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, there is a compelling need for novel delivery vehicles for different tissues and types of nucleic acids.

The purpose of this 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.   

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.