Biotechnology

HuidaGene Therapeutics creates the world’s first guanine-based editor

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HuidaGene Therapeutics, a clinical-stage genome editing company, said National Science Review had published data from its study of the world’s first DNA base editor that converts guanine to cytosine/thymine (pyrimidine), or G-to-Y.

The company has filed an international patent application for a guanine-based glycosylase (gGBE) base editor and has exclusive global rights to the underlying patent.

DNA base editors that are widely used today primarily integrate programmable DNA-binding proteins (variant Cas9, Cas12, or TALE proteins) with base deaminase (variant cytidine deaminase or adenosine deaminase). There are mainly two types of base editors: ABE (adenine base editor) and CBE (cytosine base editor), which can realize A-to-G and C-to-T transitions between 1-2 bases.

However, there are currently no base editors to edit G or T directly, because the deamination of G rarely causes base conversion, whereas T lacks amino groups, making it a challenge to overcome these limitations and develop new classes of base editors. Therefore, there is still a need to edit the G or T in most cases.

“Following our publication in Nature Biotechnology earlier this year of the independently developed and programmable A-to-Y DNA base editor, AYBE (adenine transversion base editor), we are pleased that National Science Review is publishing our paper sharing this comprehensive data. for our invention of the world’s first guanine-based base editor, gGBE,” said Xuan Yao, co-founder and CEO of HuidaGene.

CRISPR-Cas9

“CRISPR-Cas9-based CBEs and ABEs can efficiently mediate C-to-T and A-to-G substitutions. gGBE transforming G-to-Y has great potential for gene-editing drug development, and our successful development of gGBE further strengthens the Company’s intellectual property layout in the global gene-editing field.”

“Currently, all base editors require an A or C deamination reaction as a first step to trigger the next DNA repair process and achieve the goal of base editing. The deaminase present cannot catalyze guanosine and thymidine in genomic DNA to other nucleosides; therefore, direct editing of guanosine and thymidine is a major bottleneck for gene editing,” said Hui Yang, co-founder, chief scientific adviser, and chair of SAB at HuidaGene.

“Our publication titled, ‘Programmable deaminase-free base editors for G-to-Y conversion by engineered glycosylase’, from the world’s first guanine-based editor, gGBE, via our HGPRECISE platform, has demonstrated guanine editing efficiencies of up to 90% with editing in beyond the lower targets, setting the foundation for developing a new class of basic editors based on glycosylase. A new class of engineered glycosylase base editors can further enrich basic editing tools, create disease models, and develop gene editing therapies.

About HGPRECISE HuidaGene Therapeutics

HuidaGene’s HGPRECISE (HuidaGene – Platform for Rational Engineering of CRISPR-Cas Identification by Synergic Expertise) platform enables rapid discovery of Cas proteins using artificial intelligence (AI) and deep machine learning (ML) of DNA sequencing and assembly prediction from metagenomic databases.

The Cas protein generated by HGPRECISE has demonstrated superior editing efficiency, and lower off-target editing activity, compared to the widely used CRISPR-Cas9. A series of engineering transformations, protein evolution, mutation screening and validation on gGBE were performed on the HGPRECISE platform.

Last year, Japanese company EditForce created the world’s first RNA editing technology that allows the base of RNA editing to be changed from U (uracil) to C (cytosine).

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