Dyne Therapeutics FORCE Platform Achieves 75% MAPT RNA Knockdown in NHP
Dyne Therapeutics will present preclinical data at the 2026 ASGCT meeting showing its FORCE platform crossed the blood-brain barrier to knock down MAPT RNA by 75% in nonhuman primates using optimized antibody-siRNA conjugates. Subcutaneous dosing matched intravenous delivery with widespread brain distribution.
1. Upcoming ASGCT Presentation
Dyne Therapeutics will present new preclinical findings at the American Society of Gene & Cell Therapy annual meeting on May 13, 2026, highlighting the capability of its FORCE platform to penetrate the blood-brain barrier and silence MAPT RNA in the central nervous system.
2. Conjugate Design and MAPT Knockdown
The studies evaluated two antibody-siRNA conjugates: Conjugate 1 uses the clinically validated TfR1-binding Fab from ongoing neuromuscular programs, while Conjugate 2 incorporates an optimized Fab for enhanced CNS delivery. Both achieved robust MAPT RNA knockdown in mice and nonhuman primates, with Conjugate 2 reaching approximately 75% reduction.
3. Delivery Routes and Brain Distribution
Subcutaneous administration in mice produced equivalent MAPT knockdown to intravenous dosing, and both delivery routes in nonhuman primates yielded widespread and consistent distribution across deep brain regions, underscoring flexible dosing options.
4. Strategic Next Steps
While continuing advancement of clinical DMD and DM1 programs and other neuromuscular preclinical candidates, Dyne is evaluating further development of its CNS-targeted conjugates to optimize capital efficiency and maximize shareholder value in potential neurological indications.