In a new review article published in Advanced Drug Delivery Reviews, NMIN researchers and colleagues discuss the use of state-of-the-art lipid nanoparticle (LNP) technology for therapeutic gene regulation in the liver.
LNP technology enables the delivery of nucleic acids to treat liver diseases, addressing the root causes of these diseases by targeting their genetic blueprints.
“Nucleic acid therapeutics are highly specific and have the potential to achieve long-lasting or even curative effects through gene inhibition, addition, replacement, or editing,” observes co-author Dr. Jayesh Kulkarni, the inaugural recipient of the NMIN Postdoctoral Fellowship Award in Gene Therapy.
The article surveys the development, achievements and future potential of LNP technology for hepatic gene therapy, in a discussion that encompasses such considerations as the liver’s microanatomy, formulation design parameters, production methods, preclinical development and clinical translation.
As the authors detail, decades of designing lipid-based delivery systems culminated in the 2018 FDA approval of ONPATTRO™, the first-ever siRNA nanomedicine for treating hereditary amyloidogenic transthyretin (ATTRv) amyloidosis – a devastating genetic disorder characterized by abnormal deposits in the body’s organs. The laboratory of Dr. Pieter Cullis, NMIN’s Scientific Director and CEO, contributed to the LNP technology behind ONPATTRO’s success.
The authors also describe various LNP-delivered mRNA therapeutics currently under development.
“LNP delivery systems are currently at the forefront of global COVID-19 vaccine efforts,” comments co-author Dr. Dominik Witzigmann, Research Fellow at The University of British Columbia and Operational Lead for NMIN’s NanoCore Core Facility, “and we expect that LNP-based gene therapies will become increasingly integrated into mainstream medicine in the years to come.”