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GeneLeap Presents the Synthesis of a Novel GalNAc at ACS 2021

2021 / 04 / 26 Publisher:Luye Life Sciences Group

GeneLeap Biotech, a subsidiary of Luye Life Sciences specializing in the development of nucleic acid therapeutics, presented an e-poster entitled‘Design and synthesis of novel GalNAc linker moieties, conjugation to antisense oligonucleotides and evaluation in mice’ at the Spring Meeting of the American Chemical Society (ACS) 2021. The study reported new synthetic methodologies for the synthesis of novel tri-antennary GalNAc units and their evaluation for delivery and efficacy as GalNAc-antisense oligo conjugates in mice.

The results showed that the novel GalNAc moieties are more convenient and affordable.Compared with the traditional GalNAc, the novel GalNAc has a similar effect on hepatic delivery in rodents and can be used for clinical development of ASO, siRNA and other nucleic acid-based drug candidates for liver diseases.

As one of the world’s largest scientific organizations, ACS is at the forefront of evolving worldwide chemistry, and the premier professional home for chemists, chemical engineers and related professionals around the globe. The ACS Spring 2021 is being held online from April 5 to 30.

GalNAc is an amino sugar derivative of galactose. Tri-antennary GalNAc has a high affinity for the asialoglycoprotein receptor (ASGPR) that is selectively expressed on hepatocytes. The ASGPR delivers the corresponding ligands into the hepatocytes through endocytosis. Therefore, the incorporation of the current novel tri-antennary GalNAc units into oligonucleotide-based drugs selectively delivers to the liver. However, the synthesis of tri-antennary GalNAc, currently applied in clinical trials, is time-consuming and expensive due to the multistep process. The new facile methodologies developed at GeneLeap Biotech facilitate faster access to less expensive GalNAc moieties for bringing liver disease targeted nucleic acid therapeutics to patients with unmet medical need.

The preclinical study conjugated the new tri-antennary GalNAc to gapmers and evaluated their efficacy in mice as antisense oligonucleotide conjugates. The results demonstrated that the new tri-antennary GalNAc conjugates of ApoB antisense gapmers showed potent knockdown of ApoB protein in the mice plasma following subcutaneous administration. The knockdown efficiency and the duration of the new GalNAc-oligos are similar to or better than a standard tri-antennary GalNAc moiety that is currently used in clinical trials.

We are glad to see that GeneLeap Biotech has developed synthesis of single units of GalNAc and their convenient incorporation as clusters of three during oligonucleotide synthesis, which is less time-consuming, more affordable, and more convenient,” said Dr. Jason Zhang, CSO of GeneLeap Biotech. “This study could be of great value in developing liver targeted oligonucleotide-based drug candidates. In the longer term, this might lead to the clinical development of more affordable products, such as ASO, siRNA and other nucleic acid-based drug candidates for liver diseases."

GalNAc technology is the mainstream nucleic acid delivery technology. GeneLeap Biotech has built a self-developed GalNAc delivery technology platform, and mastered advanced liver-targeted delivery technology in the field of nucleic acid drug therapy, which can effectively deliver nucleic acid drugs to liver lesions and bring benefits to patients.

"We are delighted to see that this new technology adds value to the company’s IP portfolio, and we are looking forward to external collaboration to further develop this technology. With the advance of clinical practice and the maturity of GalNAc technology, GeneLeap Biotech will actively explore the development of nucleic acid-based drugs for unmet clinical needs, and bring breakthrough treatment solutions for patients with liver disorders all over the world,” said Dr. Sean Fu, CEO of GeneLeap Biotech."

About GeneLeap Biotech
GeneLeap Bio., a subsidiary of Luye Life Sciences, specializes in developing gene therapy drugs for cancer and severe infectious diseases, including mRNA and oligonucleotides. Currently, GeneLeap Biotech has R&D operations in both the USA (Boston) and China (Nanjing, Yantai).

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