GalNAc-siRNA conjugates: Prospective tools on the frontier of anti-viral therapeutics

Lokesh Thangamani; Balamuralikrishnan Balasubramanian; Murugesh Easwaran; Jeyakumar Natarajan; Karthika Pushparaj; Arun Meyyazhagan; Shanmughavel Piramanayagam

doi:10.1016/j.phrs.2021.105864

GalNAc-siRNA conjugates: Prospective tools on the frontier of anti-viral therapeutics

Pharmacol Res. 2021 Nov:173:105864. doi: 10.1016/j.phrs.2021.105864. Epub 2021 Aug 30.

Authors

Lokesh Thangamani¹, Balamuralikrishnan Balasubramanian², Murugesh Easwaran³, Jeyakumar Natarajan⁴, Karthika Pushparaj⁵, Arun Meyyazhagan⁶, Shanmughavel Piramanayagam⁷

Affiliations

¹ Computational Biology Lab, Department of Bioinformatics, Bharathiar University, Coimbatore 641046, Tamil Nadu, India.
² Department of Food Science and Biotechnology, College of Life Science, Sejong University, Seoul 05006, South Korea.
³ International Centre for Genetic Engineering and Biotechnology, New Delhi 110067, India.
⁴ Data Mining and Text Mining Laboratory, Department of Bioinformatics, Bharathiar University, Coimbatore 641046, Tamil Nadu, India.
⁵ Department of Zoology, School of Biosciences, Avinashilingam Institute for Home Science and Higher Education for Women, Coimbatore 641043, Tamil Nadu, India.
⁶ Department of Life Sciences, CHRIST (Deemed to be University), Bengaluru 560029, Karnataka, India. Electronic address: arun.meyyazhagan@res.christuniversity.in.
⁷ Computational Biology Lab, Department of Bioinformatics, Bharathiar University, Coimbatore 641046, Tamil Nadu, India. Electronic address: shanmughavel@buc.edu.in.

Abstract

The growing use of short-interfering RNA (siRNA)-based therapeutics for viral diseases reflects the most recent innovations in anti-viral vaccines and drugs. These drugs play crucial roles in the fight against many hitherto incurable diseases, the causes, pathophysiologies, and molecular processes of which remain unknown. Targeted liver drug delivery systems are in clinical trials. The receptor-mediated endocytosis approach involving the abundant asialoglycoprotein receptors (ASGPRs) on the surfaces of liver cells show great promise. We here review N-acetylgalactosamine (GalNAc)-siRNA conjugates that treat viral diseases such as hepatitis B infection, but we also mention that novel, native conjugate-based, targeted siRNA anti-viral drugs may also cure several life-threatening diseases such as hemorrhagic cystitis, multifocal leukoencephalopathy, and severe acute respiratory syndrome caused by coronaviruses and human herpes virus.

Keywords: GalNac conjugate; Hepatitis B; Hepatocytes; SiRNA; Virus.

Publication types

Review

MeSH terms

Acetylgalactosamine / administration & dosage*
Animals
Humans
RNA Interference
RNA, Small Interfering / administration & dosage*
Virus Diseases / genetics
Virus Diseases / therapy*
Viruses / classification
Viruses / genetics

Substances

RNA, Small Interfering
Acetylgalactosamine