Authors :
Presenting Author: Min Liu, PhD – RecoRNA Bio
Rui Zhang, Ph.D. – RecoRNA Bio
Rong Xin, MD – RecoRNA Bio
Wenbing Yang, Ph.D. – RecoRNA Bio
Yongheng Hou, Ph.D. – RecoRNA Bio
Yang yang, MS – RecoRNA Bio
Jin Li, Ph.D. – RecoRNA Bio
Lijun Xu, MS – RecoRNA Bio
Haojie Zhang, MS – RecoRNA Bio
Qiang Li, Ph.D. – RecoRNA Bio
Rationale: Dravet syndrome (DS) is a severe, early-onset developmental and epileptic encephalopathy primarily caused by loss-of-function mutations in the SCN1A gene, which encodes the voltage-gated sodium channel Nav1.1. Current therapies provide partial seizure control but do not address the underlying genetic defect, and patients continue to experience substantial cognitive and developmental impairment. There remains a pressing need for disease-modifying approaches that can restore Nav1.1 function and improve long-term neurological outcomes. RNA editing therapy represents an emerging modality that harnesses endogenous adenosine deaminases acting on RNA (ADARs) to modify specific sites at the transcript level, thereby enabling restoration of protein expression and/or function without permanent genomic alteration. Building on clinical advances of RNA editing in other therapeutic areas, we developed RC001, a novel RNA editing drug candidate designed to upregulate Nav1.1 protein expression in DS.
Methods: RC001 employs a chemically optimized guide RNA that recruits endogenous ADAR enzymes to specifically edit SCN1A transcripts. Preclinical efficacy and safety studies were performed in multiple systems. In a DS mouse model, we evaluated biomarker changes, seizure frequency, and seizure severity following RC001 administration. Safety assessments were conducted in rats, and both safety and pharmacodynamic studies were performed in non-human primates (NHPs). SCN1A mRNA and Nav1.1 protein levels were quantified across brain regions to confirm target engagement.
Results:
In DS mice, RC001 treatment resulted in upregulation of both SCN1A mRNA and Nav1.1 protein. This molecular correction translated into measurable improvement in disease-relevant biomarkers and a marked reduction in both frequency and severity of seizures. Safety studies in rats demonstrated a favorable safety profile with no drug-related adverse findings. In NHPs, RC001 administration was well tolerated and associated with broad distribution of the editing activity across multiple brain regions, resulting in elevated Nav1.1 protein expression. Collectively, these findings provide strong evidence of efficacy, safety, and translatability of RC001 across species.
Conclusions:
RC001 is a first-in-class RNA editing therapeutic designed to address the root cause of Dravet syndrome by restoring Nav1.1 expression. Our preclinical studies demonstrate that RC001 effectively improves seizure phenotypes in DS mice while maintaining a favorable safety profile in rats and NHPs. Importantly, the observed increase of Nav1.1 expression across multiple brain regions in higher species supports the translational potential of this therapeutic strategy. Based on these encouraging findings, we are currently advancing RC001 into investigator-initiated trials (IITs) in China to further evaluate its safety and therapeutic potential in patients with Dravet syndrome.
Funding: private funding