Gene Delivery Strategies to Promote Spinal Cord Repair

Abstract

Gene therapies hold great promise for the treatment of many neurodegenerative disorders and traumatic injuries in the central nervous system. However, development of effective methods to deliver such therapies in a controlled manner to the spinal cord is a necessity for their translation to the clinic. Although essential progress has been made to improve efficiency of transgene delivery and reduce the immunogenicity of genetic vectors, there is still much work to be done to achieve clinical strategies capable of reversing neurodegeneration and mediating tissue regeneration. In particular, strategies to achieve localized, robust expression of therapeutic transgenes by target cell types, at controlled levels over defined time periods, will be necessary to fully regenerate functional spinal cord tissues. This review summarizes the progress over the last decade toward the development of effective gene therapies in the spinal cord, including identification of appropriate target genes, improvements to design of genetic vectors, advances in delivery methods, and strategies for delivery of multiple transgenes with synergistic actions. The potential of biomaterials to mediate gene delivery while simultaneously providing inductive scaffolding to facilitate tissue regeneration is also discussed.

Efficiency and cytotoxicity analysis of cationic lipids-mediated gene transfection into AGS gastric cancer cells

“…In general, strategies used for delivery of expression cassettes into mammalian cells can be categorized into three groups, including (i) viral vectors such as adenovirus, retrovirus and lentivirus; (ii) non-viral vectors (so-called chemical-mediated techniques) such as calcium phosphate, DEAE-dextran, cationic lipids and polymers and peptides; and (iii) physical methods for direct delivery of gene into the cytoplasm (e.g. electroporation, bombardment, and microinjection) [1,2]. Different parameters can influence the selection of gene delivery method, including transfection efficiency and performance, cell toxicity and viability, cell type (primary cell or cell line), cellular context (in vivo, in vitro, ex vivo), transgenic capacity, type of genetic material (DNA, siRNA and mRNA), application purpose(s), reproducibility, general safety, ease of use, and cost-and time-effectiveness [3][4][5].…”

Cationic, amphiphilic copolymer micelles as nucleic acid carriers for enhanced transfection in rat spinal cord

“…Delivery of therapeutic nucleic acids capable of changing gene expression levels offers a promising approach to overcome these barriers. [17, 18]…”

Drug delivery, cell-based therapies, and tissue engineering approaches for spinal cord injury

“…The complexity of SCI provides numerous gene targets as potential treatments, such as nerve growth factors (NGF, BDNF, NT-3), regenerative cell adhesion molecules (L1, membrane-crossing mimetic peptide, plasticity-associated polysialylated neural cell adhesion molecule (PSA-NCAM)), Rho kinase inhibitors (Y-27632), transcription factors (BDNF, NT3), signaling molecules (cAMP), Nogo and LINGO-1 (182). From the point of view of tissue engineering, gene therapy for SCI could be realized in two ways: either transgenic cells delivered by supporting biomaterials as discussed above, or genetically modified tissue engineered biomaterials or scaffolds (183). PLGA scaffold loaded with NT-3 or BDNF encoding Lentivirus, significantly increased density of regenerating axons and myelination (184).…”