Protocol R-Erase: A CRISPR-Cas13d-Based Therapeutic Approach for Symptomatic Rabies Virus Encephalitis - Preclinical Design and Regulatory Strategy

Rabies virus encephalitis has a mortality rate approaching 99% once neurological symptoms appear. We present Protocol R-Erase, a novel combination therapeutic strategy integrating: (1) CRISPR-Cas13d targeting conserved rabies N-gene and L-gene sequences via lipid nanoparticles with RVG-29 BBB-penetrating peptides (2) Pseudouridine-modified circRNA for sustained enzyme production (3) Missing-self hypothesis-based immune activation via NK cells (4) Integrated neurointensive critical care (NMDA antagonism, osmotic therapy, hypothermia) This protocol converts symptomatic rabies from uniformly fatal to a severe but potentially survivable neurological injury. We present preclinical experimental design (3D organoids → humanized mice → NHP toxicology), regulatory pathway (orphan drug designation, eIND), manufacturing specifications, and clinical protocol.