RNA Modifications Driving Oncogenesis (RNAMoDO; U01 Clinical Trial Not Allowed) | RFA CA 24 029

Opportunity Information: Apply for RFA CA 24 029

The RNA Modifications Driving Oncogenesis (RNAMoDO) funding opportunity (RFA-CA-24-029) is an NIH cooperative agreement (U01) designed to push forward mechanistic cancer research focused on how RNA chemical modifications reshape translation in ways that promote tumor development and therapy resistance. The central idea is that RNA modifications are not just passive marks on RNA, but active regulators of gene expression and protein production. When these marks become dysregulated, they can help create or sustain cancer phenotypes. This program is specifically aimed at understanding how dynamic changes in RNA modifications reprogram the "translatome" (the set of mRNAs being translated and the way translation is executed) during tumor initiation, progression, and adaptation to treatment.

A key scientific emphasis of RNAMoDO is that translation is influenced by modifications across multiple RNA classes, not only messenger RNA (mRNA) but also transfer RNA (tRNA) and ribosomal RNA (rRNA). Recent evidence suggests that modifications in each of these RNA types can alter translation efficiency, fidelity, codon-specific decoding, ribosome behavior, and selective protein synthesis programs that cancer cells rely on. Despite growing interest in the field, the opportunity notes a major gap: the molecular mechanisms that connect changing RNA modification landscapes to large-scale translational rewiring in cancer are still poorly understood. RNAMoDO is intended to address that gap with rigorous mechanistic work rather than descriptive profiling alone.

Another defining feature of the initiative is its requirement to move beyond single-modification or single-RNA-species approaches. Historically, many labs have focused on one modification type (for example, a mark on mRNA) or one RNA class in isolation. RNAMoDO takes the position that fully explaining how translation is reprogrammed in cancer will often require integrated expertise spanning mRNA, tRNA, and rRNA biology, translational regulation, and cancer biology. Because that breadth is hard for any single lab to cover, the program strongly encourages collaborative team science and notes a preference for multi-PI (MPI) project structures where appropriate.

To be considered responsive, proposed projects must directly investigate how RNA modifications in mRNA, tRNA, and rRNA can drive oncogenesis through translational reprogramming. In addition, each project must examine interactions among modifications, including interplay between marks on the same RNA molecule (for example, combinatorial effects along an mRNA) and interactions across different RNA molecules (for example, how tRNA or rRNA modifications influence the translation of particular modified mRNAs). This emphasis on cross-talk is a core part of the program’s rationale: the translation machinery is a coupled system, and RNAMoDO is looking for mechanistic explanations that reflect that coupled biology.

Administratively, this is a discretionary NIH funding opportunity in the health domain, using the cooperative agreement mechanism, which typically means NIH program staff will have substantial involvement in project coordination, milestones, and overall direction compared with standard investigator-initiated grants. The opportunity is explicitly labeled "Clinical Trial Not Allowed," signaling that the supported research should be basic or preclinical mechanistic work rather than prospective studies assigning human participants to interventions. The original application closing date listed is 2024-11-04.

Eligibility is broad across many U.S.-based organization types, including state, local, and tribal governments; public and private institutions of higher education; nonprofits (with or without 501(c)(3) status); for-profit organizations (including small businesses); and other eligible entities. The announcement highlights additional applicant categories such as HBCUs, Hispanic-serving institutions, tribally controlled colleges and universities, Alaska Native and Native Hawaiian-serving institutions, and AANAPISI institutions, among others. Non-domestic (non-U.S.) entities are not eligible to apply, and non-domestic components of U.S. organizations are not eligible. However, foreign components, as defined by NIH policy, are allowed, meaning a U.S. applicant organization can include certain well-justified international elements within the project under NIH rules.

In practical terms, RNAMoDO is a team-oriented cancer biology program aimed at uncovering cause-and-effect mechanisms linking RNA modification changes across mRNA, tRNA, and rRNA to selective translation programs that enable cancer cells to form, evolve, and resist therapy. The opportunity is looking for integrative, mechanistic, translation-centered research that can explain not only which modifications change in cancer, but how combinations of those changes functionally rewire protein synthesis to drive oncogenesis.

• The National Institutes of Health in the education, health sector is offering a public funding opportunity titled "RNA Modifications Driving Oncogenesis (RNAMoDO; U01 Clinical Trial Not Allowed)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.393, 93.394, 93.395, 93.396, 93.399.
• This funding opportunity was created on 2024-07-29.
• Applicants must submit their applications by 2024-11-04. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
• Eligible applicants include: State governments, County governments, City or township governments, Special district governments, Independent school districts, Public and State controlled institutions of higher education, Native American tribal governments (Federally recognized), Public housing authorities/Indian housing authorities, Native American tribal organizations (other than Federally recognized tribal governments), Nonprofits having a 501 (c) (3) status with the IRS, other than institutions of higher education, Nonprofits that do not have a 501 (c) (3) status with the IRS, other than institutions of higher education, Private institutions of higher education, For-profit organizations other than small businesses, Small businesses, Others.

Apply for RFA CA 24 029

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