Current advances in non‐viral gene delivery systems: Liposomes versus extracellular vesicles

Abstract

In the past decade, nucleic acid-based drugs have emerged as an extremely promising approach for silencing specific disease-related genes and targeting undruggable ones. However, most nucleic acid drug therapies have not advanced to clinical practice due to their poor stability against serum enzyme degradation and cytotoxicity. Nanoscale drug delivery vehicles show potential to improve efficacy of nucleic acid drugs via targeted delivery to diseasecausing genes, yet, safe and efficient nanocarriers remain elusive. Lipidbased nanoparticles such as liposomes (LSs) and extracellular vesicles (EVs) are among the most extensively exploited nanoscale vehicles for therapeutic cargo delivery. LS-based nucleic acid therapies have been used for several years, with many already adopted to the clinic. More recently, EVs hold considerable promise as nucleic acid delivery vehicles due to their high biocompatibility, low immunogenicity, and the inherent abilities to interact with target cells and cross biological barriers. Moreover, a novel LS/EV hybrid gene delivery system has been engineered to preserve the benefits of both systems and generate an advanced drug delivery system. The current review focuses specifically on LS-and EV-based gene therapies and provides the key advantages and shortcomings of these systems with particular emphasis on their potential use as therapeutic vectors.Zakia Belhadj and Yunkai Qie contributed equally to this work.This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Chiral Cell Nanomechanics Originated in Clockwise/Counterclockwise Biofunctional Microarrays to Govern the Nuclear Mechanotransduction of Mesenchymal Stem Cells

“…In particular, transcription cofactor YAP will give a response to biomechanical tension along with the stretched direction . YAP nuclear translocation may be related to cytoskeleton parallel stretch, FA kinase activation, and zyxin relocation by anisotropic cell nanomechanics. , Cell nanomechanics has been reported to suppress cell senescence and aging by the inhibition of cGAS-STING signaling due to YAP/TAZ mechanotransduction. , In addition, the nuclear shape is changed by cytoskeleton force to regulate chromatin remodeling and phenotype alternation. − Therefore, in this study, the nuclear DNA synthesis level could be regulated by the mechanotransduction from anisotropic YAP signaling and biased cell nanomechanics due to chiral FA formation and heterogeneous cytoskeleton assembly (Figure ).…”

“…53,54 Cell nanomechanics has been reported to suppress cell senescence and aging by the inhibition of cGAS-STING signaling due to YAP/TAZ mechanotransduction. 55,56 In addition, the nuclear shape is changed by cytoskeleton force to regulate chromatin remodeling and phenotype alternation. 57−59 Therefore, in this study, the nuclear DNA synthesis level could be regulated by the mechanotransduction from anisotropic YAP signaling and biased cell nanomechanics due to chiral FA formation and heterogeneous cytoskeleton assembly (Figure 7).…”

Nucleic Acid Delivery Nanotechnologies for In Vivo Cell Programming

“…66,67 Being a form of cell secretion, EVs are present as a heterogeneous mixture of vesicles typically divided into major subgroups by size, including exosomes (∼30−200 nm), microvesicles (∼200− 1000 nm), and apoptotic bodies (>1000 nm). 65 EVs typically have key surface markers that are enriched, including tetraspanins (such as CD9, CD81, CD63), integrins, or adhesion molecules. 65,68 Depending on the source cell and the biogenesis process, EVs possess some endogenous homing capacity to specific target cells and also can be easily internalized into target cells by a variety of uptake mechanisms.…”

“…65 EVs typically have key surface markers that are enriched, including tetraspanins (such as CD9, CD81, CD63), integrins, or adhesion molecules. 65,68 Depending on the source cell and the biogenesis process, EVs possess some endogenous homing capacity to specific target cells and also can be easily internalized into target cells by a variety of uptake mechanisms. 65,69 and relatively nonimmunogenic due to their autologous composition from self-biomolecules and their natural function in transferring nucleic acids.…”

“…65,68 Depending on the source cell and the biogenesis process, EVs possess some endogenous homing capacity to specific target cells and also can be easily internalized into target cells by a variety of uptake mechanisms. 65,69 and relatively nonimmunogenic due to their autologous composition from self-biomolecules and their natural function in transferring nucleic acids. 65,66,69 The main disadvantages of EVs include their low loading efficiency, limited targeting specificity, and limited large-scale manufacturing.…”