Barriers to Non-Viral Vector-Mediated Gene Delivery in the Nervous System

Abstract

Efficient methods for cell line transfection are well described, but, for primary neurons, a high-yield method different from those relying on viral vectors is lacking. Viral transfection has several drawbacks, such as the complexity of vector preparation, safety concerns, and the generation of immune and inflammatory responses when used in vivo. However, one of the main problems for the use of non-viral gene vectors for neuronal transfection is their low efficiency when compared with viral vectors. Transgene expression, or siRNA delivery mediated by non-viral vectors, is the result of multiple processes related to cellular membrane crossing, intracellular traffic, and/or nuclear delivery of the genetic material cargo. This review will deal with the barriers that different nanoparticles (cationic lipids, polyethyleneimine, dendrimers and carbon nanotubes) must overcome to efficiently deliver their cargo to central nervous system cells, including internalization into the neurons, interaction with intracellular organelles such as lysosomes, and transport across the nuclear membrane of the neuron in the case of DNA transfection. Furthermore, when used in vivo, the nanoparticles should efficiently cross the blood-brain barrier to reach the target cells in the brain.

The role of surface charge in cellular uptake and cytotoxicity of medical nanoparticles

“…Toxicology. 2012;291(1-3):8. clathrin-independent and caveolae-independent pathways is used [150][151][152][153] (Figure 2, adapted from Perez-Martinez et al 154 ). The endocytic routes described so far are receptormediated and transport with high efficiency.…”

Nanoparticles for Brain-Specific Drug and Genetic Material delivery, Imaging and Diagnosis

“…Once inside the cell, dendrimers act as a proton sponge due to the presence of secondary and tertiary amines on their surface. They escape from endosomes and lysosomes, releasing their cargo to the cytosol [50]. Depending on the charge of the functional groups present at the surface, dendrimers can be divided mainly into polycationic dendrimers, able to form polyplexes with nucleic acids at physiological pH and polyanionic dendrimers, able to bind cationic drugs or to coordinate into platinum complexes [51].…”

Endosomal Escape Pathways for Non-Viral Nucleic Acid Delivery Systems

“…However, the delivery efficiency of non-viral vectors is generally poor (Pérez-Martínez, Guerra et al 2011). To enhance transfection efficiency, substantial efforts have been made to elicit effective endosomal escape.…”