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Mechanisms and challenges of nanocarriers as non-viral vectors of therapeutic genes for enhanced pulmonary delivery
J Control Release. 2022 Nov 10:S0168-3659(22)00739-8. doi: 10.1016/j.jconrel.2022.10.061. Online ahead of print.ABSTRACTWith the rapid development of biopharmaceuticals and the outbreak of COVID-19, the world has ushered in a frenzy to develop gene therapy. Therefore, therapeutic genes have received enormous attention. However, due to the extreme instability and low intracellular gene expression of naked genes, specific vectors are required. Viral vectors are widely used attributed to their high transfection efficiency. However, due to the safety concerns of viral vectors, nanotechnology-based non-viral vectors have attrac...
Source: Cancer Control - November 13, 2022 Category: Cancer & Oncology Authors: Hezhi Wang Lu Qin Xin Zhang Jian Guan Shirui Mao Source Type: research

The role of lipid components in lipid nanoparticles for vaccines and gene therapy
Adv Drug Deliv Rev. 2022 Jul 1:114416. doi: 10.1016/j.addr.2022.114416. Online ahead of print.ABSTRACTLipid nanoparticles (LNPs) play a key role in mRNA vaccines against COVID-19. In addition, many preclinical and clinical studies, including the siRNA-LNP product, Onpattro®, highlight that LNPs unlock the potential of nucleic acid-based therapies and vaccines. To understand how this 'key' works, we need to learn about the building blocks that constitute LNPs. In this review, we discuss what each lipid component adds to the LNP delivery platform in terms of size, structure, stability, apparent pKa, nucleic acid encapsulati...
Source: Advanced Drug Delivery Reviews - July 5, 2022 Category: Drugs & Pharmacology Authors: Camilla Hald Albertsen Jayesh Kulkarni Dominik Witzigmann Marianne Lind Karsten Petersson Jens B Simonsen Source Type: research

Delivery Strategies for mRNA Vaccines
AbstractThe therapeutic potential for messenger RNA (mRNA) in infectious diseases and cancer was first realized almost three decades ago, but only in 2018 did the first lipid nanoparticle-based small interfering RNA (siRNA) therapy reach the market with the United States Food and Drug Administration (FDA) approval of patisiran (Onpattro ™) for hereditary ATTR amyloidosis. This was largely made possible by major advances in the formulation technology for stabilized lipid-based nanoparticles (LNPs). Design of the cationic ionizable lipids, which are a key component of the LNP formulations, with an acid dissociation constan...
Source: Pharmaceutical Medicine - January 30, 2022 Category: Drugs & Pharmacology Source Type: research