Affiliation:
1. Faculty of Pharmaceutical Sciences University of British Columbia Vancouver British Columbia Canada
2. Center of Biological Design, Berlin Institute of Health at Charité Universitätsmedizin Berlin Berlin Germany
3. Department of Infectious Diseases and Respiratory Medicine Charité – Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin and Humboldt Universität zu Berlin Berlin Germany
4. Max‐Delbrück Center for Molecular Medicine in the Helmholtz Association Berlin Germany
Abstract
AbstractGene therapies have the potential to target and effectively treat a variety of diseases including cancer as well as genetic, neurological, and autoimmune disorders. Although we have made significant advances in identifying non‐viral strategies to deliver genetic cargo, certain limitations remain. In general, gene delivery is challenging for several reasons including the instabilities of nucleic acids to enzymatic and chemical degradation and the presence of restrictive biological barriers such as cell, endosomal and nuclear membranes. The emergence of lipid nanoparticles (LNPs) helped overcome many of these challenges. Despite its success, further optimization is required for LNPs to yield efficient gene delivery to extrahepatic tissues, as LNPs favor accumulation in the liver after systemic administration. In this mini‐review, we provide an overview of current preclinical approaches in that LNP surface modification was leveraged for cell and tissue targeting by conjugating aptamers, antibodies, and peptides among others. In addition to their cell uptake and efficiency‐enhancing effects, we outline the (dis‐)advantages of the different targeting moieties and commonly used conjugation strategies.
Funder
Mitacs
Canadian Institutes of Health Research - Antimicrobial Resistance Research Initiative
LEO Fondet
Stiftung Charité
Subject
Genetics (clinical),Drug Discovery,Genetics,Molecular Biology,Molecular Medicine