N-acetylgalactosamine delivery systems for RNA therapeutics: a patent perspective

ABSTRACT

Introduction

SiRNA molecules with a feature of good gene-silencing are critical for drug discovery and development based on RNA interference. GalNAc-RNA therapeutics is a rapid growing area in RNA therapeutics.

Areas covered

This article provides patent landscape and modification feature of GalNAc-RNA therapeutics. The US-granted patents from January 2004 to April 2023 were retrieved and analyzed.

Expert opinion

Globally, our study is the first one to holistically depict a map of modifications and therapeutic applications for GalNAc-RNA therapeutics by patent data analysis. The results showed there were 8 major modifications and 5 new emerged modifications for GalNAc-RNA therapeutic agents. Especially, the study provides recent new emerged modifications in sugar, base, and internucleotide linkage of GalNAc-RNA therapeutic agents, e.g. morpholino-type ring, 5-methylcytosine, and phosphorodithioates. In addition, our study systematically demonstrated major therapeutic applications for GalNAc-RNA therapeutics, including liver or gallbladder disorders, anticancer, antihyperlipidemics, and disorders of the nervous system etc.

KEYWORDS:

• GalNAc
• RNA
• GalNAc-RNA
• N-acetylgalactosamine
• patent

Article highlights

• Globally, our study is the first one to holistically depict a map of modifications and therapeutic applications for GalNAc-RNA therapeutics.

• Eight major modifications and five new emerged modifications are identified for GalNAc-RNA therapeutic agents.

• The study provides recent new emerged modifications in sugar, base, and internucleotide linkage of GalNAc-RNA therapeutic agents, e.g. morpholino-type ring, 5-methylcytosine, and phosphorodithioates.

• The study systematically demonstrates major therapeutic applications for GalNAc-RNA therapeutics, including liver or gallbladder disorders, anticancer, antihyperlipidemics, and disorders of the nervous system, etc.

• Sugar modifications of 2’-O-R and 2’-R are most frequently modification for GalNAc-RNA therapeutic agents.

• There are considerable similarities in developing model between GalNAc-RNA therapeutics and mRNA-LNP therapeutics, e.g. just a few companies dominate all technologies.

Declaration of interests

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contribution statement

Design, data collection and analysis, and manuscript draft by Zhang, and data collection by Wang.

Additional information

Funding

This paper was not funded.