Role of Lipid-Based and Polymer-Based Non-Viral Vectors in Nucleic Acid Delivery for Next-Generation Gene Therapy

Abstract

The field of gene therapy has experienced an insurgence of attention for its widespread ability to regulate gene expression by targeting genomic DNA, messenger RNA, microRNA, and short-interfering RNA for treating malignant and non-malignant disorders. Numerous nucleic acid analogs have been developed to target coding or non-coding sequences of the human genome for gene regulation. However, broader clinical applications of nucleic acid analogs have been limited due to their poor cell or organ-specific delivery. To resolve these issues, non-viral vectors based on nanoparticles, liposomes, and polyplexes have been developed to date. This review is centered on non-viral vectors mainly comprising of cationic lipids and polymers for nucleic acid-based delivery for numerous gene therapy-based applications.

A brain glioma gene delivery strategy by angiopep-2 and TAT-modified magnetic lipid-polymer hybrid nanoparticles

“…By contrast, non-viral vectors with low immunogenicity and relative safety have attracted extensive attention. 5,6 However, the disadvantages of non-viral vectors are poorer brain targeting and lower transfection efficiency for therapy of central nervous system diseases. 7 To improve brain targeting, the penetration efficiency of the BBB should be improved rst.…”

Advances in Lipid Nanoparticles for mRNA-Based Cancer Immunotherapy

“…Lipoplexes, consisting of cationic liposomes interacting electrostatically with the negative charges of the phosphate backbone of mRNA, were the earliest lipid-based delivery systems successfully employed to introduce mRNA molecules into target cells (Figure 1) (Felgner and Ringold, 1989;Kranz et al, 2016). However, after a first brief phase of great enthusiasm, lipoplexes have shown important concerns, such as high instability, relatively low transfection efficiency and poor customizable composition, given that they are often formulated with an excess of cationic charges not only to promote mRNA binding but also to facilitate the interaction with the anionic phospholipids in the plasma membrane and subsequently promote its uptake by endocytosis (Li and Huang, 1997;Xue et al, 2015;Guevara et al, 2019b;Wahane et al, 2020).…”

Gene therapy in Duchenne muscular dystrophy: Identifying and preparing for the challenges ahead

“…Imran Kausar highlighted that there is a hope for the future that viral vectors won't need to be used and that new technologies may allow different and better delivery mechanisms, maybe removing the immune-response issue highlighted above 13 .…”