Selective Harnessing of Intrinsic Neuroplasticity Engineering (SHINE)

The Defense Advanced Research Projects Agency Defense Sciences Office seeks innovative basic or applied research concepts in targeted neuroplasticity under the Selective Harnessing of Intrinsic Neuroplasticity Engineering (SHINE) Disruption Opportunity, with proposals due October 9, 2026, at 4:00 p.m. ET and questions due October 2, 2026, at 4:00 p.m. ET. Awards will be structured as Other Transaction Prototype Agreements, with a maximum of $2,000,000 per award inclusive of government funding and performer cost share.

The program comprises two complementary 18-month technical tracks. Track A (Accelerated Translation) requires clinical-ready prototype systems with existing safety data and regulatory pathways, demonstrated in clinical populations or translationally relevant animal models, and culminates in readiness for human clinical trials. Track B (Foundational Technology Development) pursues high-risk, proof-of-concept platforms using novel biologics, biomaterials, or engineered systems, demonstrated in vitro or in preclinical animal models, and culminates in readiness for animal testing.

Both tracks must establish circuit-selective neuroplasticity with intervention selectivity (3:1 target-to-off-target ratio), biological target engagement (2-fold increase with 20% off-target variance), and quantifiable neuroplasticity changes (effect size >0.6). Track A requires 80% targeted in vivo delivery with 10% off-target dispersion and Therapeutic Index 5 with clinical biomarkers; Track B requires 90% in vitro or preclinical spatial containment with acute plasticity proof-of-concept within 72 hours and an in vivo maturation plan.

Fixed payable milestones occur at months 3, 6, 9, 12, and 18, with month 9 as a planned program evaluation point. Proposers must host a site visit and attend a mandatory two-day virtual PI meeting at month 9. All human subject research must obtain IRB and HRPO approvals prior to proposal submission. CMMC Level 1 (Self-Assessment) certification is required for prime performers and subcontractors processing Federal Contract Information. Submissions must be unclassified, uploaded as zip files not exceeding 100 MB through DARPA's Broad Agency Announcement Tool Portal, and comply with DARPA-PA-25-07 Amendment 1 format requirements. Fundamental research is anticipated with no anticipated publication restrictions.