Engineering liposomal nanoparticles for targeted gene therapy

Abstract

Recent mechanistic studies have attempted to deepen our understanding of the process by which liposome-mediated delivery of genetic material occurs. Understanding the interactions between lipid nanoparticles and cells is still largely elusive. Liposome-mediated delivery of genetic material faces systemic obstacles alongside entry into the cell, endosomal escape, lysosomal degradation and nuclear uptake. Rational design approaches for targeted delivery have been developed to reduce off-target effects and enhance transfection. These strategies, which have included the modification of lipid nanoparticles with target-specific ligands to enhance intracellular uptake, have shown significant promise at the proof-of-concept stage. Control of physical and chemical specifications of liposome composition, which includes lipid-to-DNA charge, size, presence of ester bonds, chain length and nature of ligand complexation, is integral to the performance of targeted liposomes as genetic delivery agents. Clinical advances are expected to rely on such systems in the therapeutic application of liposome nanoparticle-based gene therapy. Here, we discuss the latest breakthroughs in the development of targeted liposome-based agents for the delivery of genetic material, paying particular attention to new ligand and cationic lipid design as well as recent in vivo advances.

Nanoparticle-based drug delivery in the inner ear: current challenges, limitations and opportunities

“…In addition, unstable drugs such as biological molecules can be stabilized within micelles and delivered to the site of interest. Liposomal NPs are another platform for drug delivery [65,66]. A liposome NP utilizes a double layer of amphipathic molecules, creating a hydrophilic external and internal surface such as that seen in a phospholipid bilayer.…”

Gene delivery by peptide-assisted transport

“…Furthermore, peptides can incorporate a variety of useful structural and functional motifs, including protein fragments with similar secondary structure features as their parent domains, and high-affinity/high-specificity cell-binding motifs selected through phage display or other high-throughput technologies. Additional advantages of peptides as compared to proteins include ease of production (in bacterial or mammalian cells, or by using solid phase peptide synthesis), and stability during storage and handling under ambient conditions [18,19]. Given their unique properties and facile production, peptides have been widely explored for their capacity to help overcome the barriers for gene delivery (Figure 2), including cell penetration, endosomal escape, and organelle targeting [19].…”

The Role of Self-Assembling Lipid Molecules in Vaccination

“…However, advances in liposome formulation are mitigating these limitations while reducing off-target effects. These new technologies are revolutionizing the DNA/RNA vaccine field and could become a viable option soon [75].…”