OutFlowGen: One-Time CRISPR Therapy for Glaucoma
About This Grant
ABSTRACT / SUMMARY Glaucoma is the leading cause of irreversible blindness, driven in most patients by elevated intraocular pressure (IOP) from increased resistance in the eye’s drainage tissue, the trabecular meshwork (TM). While IOP-lowering eye drops help, real-world adherence is poor, side effects are common, and benefits vanish when dosing lapses. This Phase I STTR develops a one-time, adherence-independent therapy: a lipid nanoparticle (LNP) encapsu- lating CRISPR/Cas9 mRNA and guides specific to ROCK1/2 delivered by an intracameral injection to the TM cells, relaxing the tissue, enhancing aqueous outflow, and thereby lowering IOP without daily medication. The approach is pathway-targeted (not mutation-specific) and is intended to benefit the broad primary open-angle glaucoma population. AIM 1 will optimize guide RNAs and LNP formulation for efficient, safe ROCK editing across high-, intermediate-, and low-flow TM regions (the latter being disproportionately expanded and stiff in glaucoma). Editing will be quantified by next-generation sequencing, and traction force, fibrotic marker, and tis- sue viability read outs will all be used to select a lead LNP-Cas9/gROCK candidate. AIM 2 will perform a head-to-head comparison in paired ex vivo perfused human glaucomatous eyes: one eye will receive a single LNP-Cas9/gROCK treatment and the fellow eye will receive daily Rhopressa (0.02% Netarsudil ophthalmic so- lution) dosing, a ROCK-inhibitor. We will measure outflow facility continuously, map segmental outflow before/af- ter treatment, and assess TM stiffness, cell-level contractility, on-target editing, and safety. Success is defined by >50% editing in the TM, <0.3% off-target editing, increases in outflow facility and IOP homeostasis, reductions in contractility and stiffness, with no safety concerns. The work is innovative in three ways: (i) nonviral LNP gene editing in anterior segment tissue; (ii) pathway-level editing to replicate a validated mechanism with durable effect; and (iii) spatially resolved linkage of molecular editing to functional and biomechanical outcomes in human donor eyes, the closest proxy to in vivo human physiology. An experienced, cross-disciplinary team in ocular gene delivery, outflow biology, biomechanics, and clinical translation will execute the plan using established cores and protocols. If successful, this project will justify IND-enabling studies in Phase II, advancing a first-in-class, one-time therapy that could transform glaucoma care by removing the adherence barrier while preserving vision.
Grant Summary
OutFlowGen: One-Time CRISPR Therapy for Glaucoma is a NEI - National Eye Institute grant providing up to $311K for university, nonprofit, healthcare org. Applications are due 2027-05-31 (open). Check eligibility and apply with FindGrants.
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How to Apply
Up to $311K
2027-05-31
- 1Confirm your organization is eligible for OutFlowGen: One-Time CRISPR Therapy for Glaucoma from NEI - National Eye Institute, checking organization type, location, and any population or project requirements.
- 2Gather the required documents and information, including your organization details, project plan, and budget figures.
- 3Draft your application narrative and budget addressing the funder's priorities and review criteria. FindGrants can draft each section for you to review and edit.
- 4Review every section against the requirements checklist, then export a submission-ready application pack and submit it to NEI - National Eye Institute before the deadline.
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OutFlowGen: One-Time CRISPR Therapy for Glaucoma: Frequently Asked Questions
Who is eligible for the OutFlowGen: One-Time CRISPR Therapy for Glaucoma?
OutFlowGen: One-Time CRISPR Therapy for Glaucoma is offered by NEI - National Eye Institute and is generally open to university, nonprofit, healthcare org. It is open to organizations nationwide unless the funder specifies otherwise. Review the specific eligibility terms before applying, since funders set their own requirements around organization type, location, and the population or project being served.
How much funding does the OutFlowGen: One-Time CRISPR Therapy for Glaucoma provide?
OutFlowGen: One-Time CRISPR Therapy for Glaucoma provides up to $311K per award from NEI - National Eye Institute. Actual award sizes depend on the scope of your project, available program funds, and the number of applicants, so build a budget that reflects realistic, allowable costs rather than the maximum figure.
When is the OutFlowGen: One-Time CRISPR Therapy for Glaucoma deadline?
Applications for OutFlowGen: One-Time CRISPR Therapy for Glaucoma are due 2027-05-31 (open). Because deadlines can change, verify the date with the funder, NEI - National Eye Institute, and give yourself enough time to prepare a complete, competitive application before the close date.
How do you apply for the OutFlowGen: One-Time CRISPR Therapy for Glaucoma?
To apply for OutFlowGen: One-Time CRISPR Therapy for Glaucoma, confirm your eligibility, gather the required documents, and prepare a narrative and budget that address the funder's priorities. FindGrants guides you step by step and can draft each section, then exports a submission-ready application pack for this grant from NEI - National Eye Institute.