All applications are due April 6, 2020, by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on the listed date(s).
Support will be provided for proof of concept studies of technologies to deliver genome editing machinery into disease relevant cells and tissues in vivo. As used here, the term "genome editing machinery" includes an editing enzyme, or other genome editing entity, as well as nucleic acids if applicable. Technologies can target either the nuclear or mitochondrial genome, or both.
Projects can focus on a single cell type, or multiple cell types. Emphasis will be placed on organs and cell types that are clinically relevant for disorders amenable to genome editing in humans but have no effective in vivo delivery technologies currently available. Because of the potential of edited stem cells to repopulate organs, technologies to deliver to stem cells are of particular interest.
For applications proposing delivery technologies for organs and cell types that are currently accessible to in vivo genome editing by available methods, emphasis will be placed on technologies that produce substantial qualitative improvements in clinical application.
Examples of qualitative improvements that would substantially enhance clinical application include, but are not limited to:
Given the propensity of the liver to take up many substances, including nucleic acids, as well as the existence of established hepatocyte-targeted delivery systems, projects focused solely on delivery to hepatocytes will have a low priority for funding, though such applications will be accepted.
This funding opportunity is limited to non-viral technologies to deliver genome editors. Non-viral vector technologies could include, but are not limited to:
Projects proposing the use of high-throughput, combinatorial, or barcoding-based screening approaches to develop cell-type specific delivery vehicles are encouraged. For proof of concept studies, investigators can choose from any programmable editors, including, but not limited to CRISPR-Cas systems, other nucleases, DNA- or RNA-targeted base editors, prime editors, recombinases, or transposases. Optimally, proposed technologies would be applicable to different types of genome editors. Applications can propose delivery of genome editors in the form of DNA, RNA, and/or protein.
All applications, including Phase I, must include plans to test delivery systems in vivo. Such studies can be carried out in normal animals, or in animal models of disease. As noted above, the primary goal of this FOA is not to develop gene editing therapies for specific diseases, but to develop delivery systems to particular cells which would be of relevance to multiple diseases resulting from genetic abnormalities in given cell type(s). However, animal models of disease can be utilized if they can be used to demonstrate delivery to target cell types.
In addition to studies in animals, applicants can also propose studies in relevant human cell systems (including organoids), if available.
Activities outside the scope of this announcement include: