Recombinant versus native botulinum neurotoxin type A: structural and pharmacodynamic comparison
Year: 2026
Type: article
Abstract: Botulinum neurotoxins (BoNTs) are highly potent exotoxins utilized for esthetic and therapeutic indications. Unlike traditional products derived from Clostridium botulinum , this study presents the design, production, structural characterization and preclinical pharmacodynamics of recombinant BoNT type A1 (rBoNT/A, YY001), newly approved by the National Medical Products Administration and the first rBoNT/A product to be licensed for commercialization in the world. Expressed in Escherichia coli and purified to greater than 99% homogeneity, YY001 shares a core amino-acid sequence with BoNT/A1 in Botox. The additional five residues at the N-terminus and six residues at the C-terminus of the light chain (LC), as well as two residues at the N-terminus of the heavy chain (HC), originate from residual amino acids after protease cleavage; mass-spectrometric peptide mapping confirmed this sequence fidelity. Cryo-electron microscopy yields a 3.2 Å resolution map of the full-length active rBoNT/A, revealing a canonical LC–H N –H C three-domain architecture that predominantly adopts an open conformation, with a root-mean-square deviation of 1.3–1.5 Å relative to native BoNT/A. In vivo head-to-head pharmacodynamic studies showed comparable potency between YY001 and Botox in both mouse digit abduction score assay and rat compound muscle action potential assays. Altogether, the structural, biochemical and pharmacological data indicate that YY001 possesses molecular and functional attributes that are highly comparable to those of native BoNT/A, while providing improved manufacturing consistency and reduced biosafety risks.
Language: English
Subfield: Clinical Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,520
OpenAlex ID: W7223217666