HuidaGene Therapeutics' Novel DNA Gene-Editing System Cas12i Patent Granted by USPTO

SHANGHAI and CLINTON, N.J., May 16, 2023 /PRNewswire/ -- HuidaGene Therapeutics (????; HuidaGene), a clinical-stage company focusing on developing gene editing tools and gene therapies, today announced that the United States Patent and Trademark Office (USPTO) has granted to the Company patent US11,649,444B1 with respect to its independently-developed DNA editing system, CRISPR-Cas12i (Cas12Max®), in just 9 months post-filing with the assistance of a reputable US law firm. Cas12Max^® has the highest DNA editing efficiency in mammalian cells compared with Streptococcus pyogenes Cas9 (SpCas9) and Lachnospiraceae bacterium Cas12a (LbCas12a). The grant of this US patent represents the first oversea breakthrough of CRISPR-Cas12i systems developed in China. This fundamental patent covers multiple novel Cas12i proteins, and their variants and DNA editing uses thereof. HuidaGene exclusively owns its global rights.

"After granting the CRISPR-Cas13X/Y (13e/f) patents in both China and US, grant of the first overseas patent of Cas12i is another important milestone for HuidaGene, which further strengthens the Company's intellectual property position," said Xuan Yao, Ph.D., Co-Founder and Chief Executive Officer of HuidaGene. "With our commitment to developing novel CRISPR systems, the Company has carried out global patent layout of the core technology and established the Company's dominant position in gene editing tool and gene therapy development. The strong intellectual property protection for our gene editing tools would allow more independent gene editing products to be commercialized globally."

CRISPR RNA and CRISPR-associated (Cas) protein constitute an RNA-guided adaptive immune system found in bacteria and archaea for the defense of virus infection. Class 2, Type II (CRISPR-Cas9) system has been transformed into one of the most powerful gene-editing tools used globally for biomedical research that has therapeutic potential against incurable genetic disorders by modifying their DNA sequences. However, DNA double-strand breaks (DSBs)-related genotoxicities due to formation of DSBs by Cas9 and DNA repair, including apoptosis, chromosome deletions, and chromosomal rearrangements, remain to be the major concern in clinical development. The in-vivo delivery of the CRISPR-Cas9 system for efficient gene editing is also challenging due to its large size. Additionally, various Cas9 patents owned by multiple patentees and continuous litigations are likely to remain unresolved for years to come, suggesting many uncertainties to commercial development.

Class 2, Type V (CRISPR-Cas12) system is an emerging CRISPR system different from Class 2, Type II (CRISPR-Cas9) system in both evolution and classification, and thus it is believed that its use is not limited to Cas9 patents.

The Company filed the patent based on the November 2022 publication describing the novel engineered xCas12i with high activity, high specificity, and board protospacer adjacent motif (PAM) range. "On 15 November 2022, my team published a research paper online of the Protein & Cell titled 'An engineered xCas12i with high activity, high specificity and board PAM range'," said Hui Yang, Ph.D., Co-Founder, Chief Scientific Advisor, and Chairman of the SAB at HuidaGene. "My team has identified 10 novel Cas12i proteins through AI and deep ML of DNA sequencing and assembly prediction from metagenomic database followed by the identification of xCas12i through the fluorescent reporting system. Through HGPRECISE^® (HuidaGene ? Platform for Rational Engineering of CRISPR-Cas Identification by Synergic Expertise) platform, we further engineered xCas12i system to develop a high-fidelity xCas12i variant (Cas12Max®), which is smaller than Cas9 allowing it to be packaged and delivered in vivo through a single AAV vector and has the highest editing efficiency in mammalian cells with strong fluorescence intensity in compared with SpCas9 and LbCas12a."

At present, HuidaGene has applied Cas12Max® to the development of in vivo gene therapy for various indications in neurology, neuromyology, and hepatology. HuidaGene will continue to improve the CRISPR-based gene-editing technology and bring safe gene-editing therapies a reality for millions of patients worldwide.

About HGPRECISE^® Platform
HuidaGene's HGPRECISE® (HuidaGene ? Platform for Rational Engineering of CRISPR-Cas Identification by Synergic Expertise) platform enables rapid discovery of Cas proteins using both artificial intelligence (AI) and deep machine learning (ML) of DNA sequencing and assembly prediction from metagenomic database. HGPRECISE^® generated Cas12i protein (Cas12Max^®) has demonstrated superior on-target editing efficiency, lower off-target editing activity compared to widely-used CRISPR-Cas9 as well as Cas12a, Cas12b and Cas12e. Furthermore, Cas12Max^® has a relatively smaller size (1033-1093 aa) compared to SpCas9 and Cas12a and has a broad 5' TN protospacer adjacent motif (PAM) preference. With its high on-target editing efficiency, low off-target editing activity, and small size for packaging into single AAV vector, Cas12Max® has many potentials and prospects in biomedical research, agriculture, gene therapy, and other fields.

About HuidaGene -????  
HuidaGene Therapeutics (????) is a global clinical-stage biotechnology company focusing on discovering, engineering, and developing gene editing tools and gene therapies to rewrite the future of genomic medicine. Based in Shanghai and New Jersey, HuidaGene is committed to addressing patients' needs globally with various preclinical therapeutic programs covering ophthalmology, otology, myology, and neurology. HuidaGene is currently advancing clinical programs in RPE65 mutation-associated inherited retinal dystrophies and various preclinical pipelines, including programs in neovascular age-related macular degeneration, retinitis pigmentosa, hereditary hearing loss, Duchenne muscular dystrophy, and MECP2 duplication syndrome. Those CRISPR-based therapeutics offer the potential to cure patients with life-threatening conditions by repairing the cause of their disease. HuidaGene is committed to transforming the future of genome-editing medicine.
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