Recent Advances in Nonviral Vectors for Gene Delivery

Abstract

CONSPECTUS Non-viral vectors, typically based on cationic lipids or polymers, are preferred due to safety concerns with viral vectors. So far, non-viral vectors can proficiently transfect cells in culture, but obtaining efficient nanomedicines is far from evident. To overcome the hurdles associated with non-viral vectors is significant for improving delivery efficiency and therapeutic effect of nucleic acid. The drawbacks include the strong interaction of cationic delivery vehicles with blood components, uptake by the reticuloendothelial system (RES), toxicity, targeting ability of the carriers to the cells of interest, and so on. PEGylation is the predominant method used to reduce the binding of plasma proteins with non-viral vectors and minimize the clearance by RES after intravenous administration. The nanoparticles that are not rapidly cleared from the circulation accumulate in the tumors due to the enhanced permeability and retention effect, and the targeting ligands attached to the distal end of the PEGylated components allow binding to the receptors on the target cell surface. Neutral or anionic liposomes have been also developed for systemic delivery of nucleic acids in experimental animal model. Designing and synthesizing novel cationic lipids and polymers, and binding nucleic acid with peptides, targeting ligands, polymers, or environmentally sensitive moieties also attract many attentions for resolving the problems encountered by non-viral vectors. The application of inorganic nanoparticles in nucleic acid delivery is an emerging field, too. Recently, different classes of non-viral vectors appear to be converging and the features of different classes of non-viral vectors could be combined in one strategy. More hurdles associated with efficient nucleic acid delivery therefore might be expected to be overcome. In this account, we will focus on these novel non-viral vectors, which are classified into multifunctional hybrid nucleic acid vectors, novel membrane/core nanoparticles for nucleic acid delivery and ultrasound-responsive nucleic acid vectors. The systemic delivery studies are highlighted. Finally, we bring forward the prospect for nucleic acid delivery. We think a better understandings of the fate of the nanoparticles inside the cell and of the interactions between the parts of hybrid particles will lead to a delivery system suitable for clinical use. We also underscore the value of sustained release of nucleic acid and presume making vectors targeted to cells with sustained release in vivo should be an interesting research challenge.

Molecular targeting of liposomal nanoparticles to tumor microenvironment

“…37 Systemic delivery of cationic liposomes encounters obstacles such as the strong interaction with blood components, uptake by the RES, kidney filtration, and toxicity. 38 If the agent to be delivered is targeted to organs other than the RES, modification of liposomes with polymers, such as polyethylene glycol (PEG), can reduce the absorption of opsonins and avoid rapid RES clearance, thus achieving a long circulation. 39 Binding of plasma proteins by liposomes is the primary mechanism for the RES to recognize circulating liposomes.…”

Chemoenzymatic Synthesis of Polypeptides for Use as Functional and Structural Materials

“…[70] These cationic star-shaped polypeptides can be used as peptide/plasmid DNA complexes for gene delivery. [116] The efficiency of gene transfection of human embryonic kidney 293 cells using a series of cationic polypeptides of this type was examined. The other type of architecture is represented by telechelic polypeptides in which two independent polypeptide chains propagate in different N-to-C directions.…”

Effect of inserted spacer in hepatic cell-penetrating multifunctional peptide component on the DNA intracellular delivery of quaternary complexes based on modular design

“…2,3 Effective gene delivery to the target sites remains a challenge because of the difficulty of transporting these negatively charged macromolecules to overcome various physical barriers without degradation. 1,4 A safe and efficient delivery system is thus needed for a successful gene therapy. 1,4,5 Since 1960s, nonviral vectors based on cationic polymers [6][7][8][9] and lipids…”

“…1,4 A safe and efficient delivery system is thus needed for a successful gene therapy. 1,4,5 Since 1960s, nonviral vectors based on cationic polymers [6][7][8][9] and lipids…”