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RfxCas13d

Development stage
Preclinical
Modality
CRISPR-Cas9 → CRISPR Systems → Programmable Nucleases → Gene Editing → Gene Therapies, RNA Therapeutics → Nucleic Acid Therapeutics
Administration
Intrathecal, Intrastriatal, Intravenous
01

Overview

**RfxCas13d**, also known as **CasRx**, is a compact CRISPR-Cas13d effector protein derived from Ruminococcus flavefaciens, widely used for programmable RNA knockdown in mammalian cells. It forms a complex with a CRISPR RNA (crRNA) guide to specifically bind and cleave target single-stranded RNAs via its two HEPN nuclease domains, without requiring a protospacer flanking sequence (PFS), enabling versatile targeting. Upon target engagement, it undergoes conformational changes activating both cis-cleavage of the target and trans-collateral cleavage of bystander RNAs, particularly when targeting abundant transcripts, which can lead to transcriptome-wide degradation, chromatin collapse, and cell proliferation defects. RfxCas13d has been delivered via AAV vectors to the CNS for gene silencing in models of amyotrophic lateral sclerosis (SOD1) and Huntington's disease (HTT), and applied in PAC-MAN strategies against SARS-CoV-2, with catalytically dead (dRfxCas13d) variants used for translation repression or editing fusions. Its small size facilitates viral delivery, though collateral activity requires careful optimization for therapeutic use.[1][2][5][7]

Other names
Cas13dCas-13dCas 13d
02

Targets

Single-stranded RNA (ssRNA) complementary to the RfxCas13d guide RNA

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