DIRECT DELIVERY OF THERAPEUTIC GENES FOR STIMULATION OF POSTTRAUMATIC NEUROGENERATION

Abstract

There were analyzed the latest developments in direct, not mediated by transplantation transfected delivery cells of therapeutic genes to stimulate posttraumatic neurogeneration. We present results of their research on two experimental models of neurotrauma. Direct one-time delivery to the damaged area of therapeutic cloning of human genes vegf and fgf2 using non-viral vectors improves post-traumatic regeneration of peripheral nerve and spinal cord. Direct injection of plasmid DNA directly into the damaged area is a little less efficient delivery of the same therapeutic genes to the cellular carriers in their immediate area of transplantation in contusion spinal cord injury, and by some measures even surpasses it. Prospects for improving the efficiency of direct gene therapy is associated with the use of synthetic platform based on biocompatible and biosoluble materials.

Keywords

neurogeneration / gene therapy / delivery of plasmid DNA

References

[1] 1. Масгутов Р.Ф., Салафутдинов И. И., Богов А.А. и др. Стимуляция посттравматической регенерации седалищного нерва крысы с помощью плазмиды, экспрессирующей сосудистый эндотелиальный фактор роста и основной фактор роста фибробластов // Клеточная трансплантология и тканевая инженерия . - 2011. - Т. 6, № 3. - С. 67-70.

[2] 2. Apfel S.C. Nerve growth factor for the treatment of diabetic neuropathy: what went wrong, what went right, and what does the future hold? // Int Rev Neurobiol. - 2002. - Vol. 50. - P. 393-413.

[3] 3. Bergen J.M., Park I.K., Horner P.J., Pun S.H. Nonviral approaches for neuronal delivery of nucleic acids // Pharm Res. - 2008. - Vol. 25, № 5. - P. 983-998.

[4] 4. Bharali D.J., Klejbor I., Stachowiak E.K. et al. Organically modified silica nanoparticles: a nonviral vector for in vivo gene delivery and expression in the brain // Proc. Natl. Acad. Sci. USA. - 2005. - Vol. 102, № 32. - P. 11539-11544.

[5] 5. Bleiziffer O.E., Friksson E., Yao Fhorch, R.E., Kneser U. Gene transfer strategies in tissue engineering // J. Cell. Mol. Med. - 2007. - Vol. 11, № 2. - P. 206-223.

[6] 6. Bonner J.F., Blesch A., Neuhuber B., Fischer I. Promoting directional axon growth from neural progenitors grafted into the injured spinal cord // J. Neurosci Res. - 2010. - Vol. 88, № 6. - P. 1182-1192.

[7] 7. Chen J., Wu J., Apostolova I., Skup M. et al. Adeno-associated virus-mediated L1 expression promotes functional recovery after spinal cord injury // Brain. - 2007. - Vol. 130, № 4. - P. 954-969.

[8] 8. Choi B.H., Ha Y., Ahn C.H. et al. A hypoxia-inducible gene expression system using erythropoietin 3' untranslated region for the gene therapy of rat spinal cord injury // Neurosci Lett. - 2007. - Vol. 412, № 2. - P. 118-122.

[9] 9. Colella P., Auricchio A. AAV-mediated gene supply for treatment of degenerative and neovascular retinal diseases // Curr. Gene Ther. - 2010. - Vol. 10, № 5. - P. 371-380.

[10] 10. da Cruz M.T., Simoes S., de Lima M.C. Improving lipoplex-mediated gene transfer into C6 glioma cells and primary neurons // Exp. Neurol. - 2004. - Vol. 187, № 1. - P. 65-75.

[11] 11. Elouahabi A., Ruysschaert J.M. Formation and intra-cellular trafficking of lipoplexes and polyplexes // Mol Ther. - 2005. - Vol. 11, № 3. - P. 336-347.

[12] 12. Haastert K., Grothe C. Gene therapy in peripheral nerve reconstruction approaches // Curr. Gene Ther. - 2007. - Vol. 7, № 3. - P. 221-228.

[13] 13. Herrera J.J. Sundberg L.M., Zentilin L. et al. Sustained expression of vascular endothelial growth factor and angiopoietin-1 improves blood-spinal cord barrier integrity and functional recovery after spinal cord injury // J. Neurotrauma. - 2010. - Vol. 27, № 11. - P. 2067-2076.

[14] 14. Huang W.C., Kuo H.S., Tsai M.J. et al. Adeno-associated virus-mediated human acidic fibroblast growth factor expression promotes functional recovery of spinal cord-contused rats // J. Gene Med. - 2011. - Vol. 13, № 5. - P. 283-289.

[15] 15. Hung K.S., Tsai S.H., Lee T.C. et al. Gene transfer of insulin-like growth factor-I providing neuroprotection after spinal cord injury in rats // J. Neurosurg Spine. - 2007. - Vol. 6, № 1. - P. 35-46.

[16] 16. Kaech S. Kim J.B., Cariola M., Ralston E. Improved lipid-mediated gene transfer into primary cultures of hippocampal neurons // Brain Res. Mol. Brain Res. - 1996. - Vol. 35, № 1-2. - P. 344-348.

[17] 17. Kane M.J., Citron B.A. Transcription factors as therapeutic targets in CNS disorders // Recent Pat. CNS Drug. Discov. - 2009. - Vol. 4, № 3. - P. 190-199.

[18] 18. Koda M., Hashimoto M., Murakami M. et al. Adenovirus vector-mediated in vivo gene transfer of brain-derived neurotrophic factor (BDNF) promotes rubrospinal axonal regeneration and functional recovery after complete transection of the adult rat spinal cord // J. Neurotrauma. - 2004. - Vol. 21, № 3. - P. 329-337.

[19] 19. Lavdas A.A., Papastefanaki F., Thomaidou D., Matsas R. Cell adhesion molecules in gene and cell therapy approaches for nervous system repair // Curr. Gene Ther. - 2011. - Vol. 11, № 2. - P. 90-100.

[20] 20. Li Y., Wang J., Lee C.G. et al. CNS gene transfer mediated by a novel controlled release system based on DNA complexes of degradable polycation PPE-EA: a comparison with polyethylenimine/DNA complexes // Gene Ther. - 2004. - Vol. 11, № 1. - P. 109-114.

[21] 21. Liu J.L., Ma Q.P., Huang Q.D. et al. Cationic lipids containing protonated cyclen and different hydrophobic groups linked by uracil-PNA monomer: synthesis and application for gene delivery // Eur. J. Med. Chem. - 2011. - Vol. 46, № 9. - P. 4133-4141.

[22] 22. Llorens F., Gil V., del Rнo J.A. Emerging functions of myelin-associated proteins during development, neuronal plasticity, and neurodegeneration // FASEB J. - 2011. - Vol. 25, № 2. - P. 463-475.

[23] 23. Lu K.W., Chen Z.Y., Hou T.S. Protective effect of liposome-mediated glial cell line-derived neurotrophic factor gene transfer in vivo on motoneurons following spinal cord injury in rats // Chin J. Traumatol. - 2004. - Vol. 7, № 5. - P. 275-279.

[24] 24. Luten J. van Nostrum C.F., De Smedt S.C., Hennink W.E. Biodegradable polymers as non-viral carriers for plasmid DNA delivery // J. Control Release. - 2008. - Vol. 126, № 2. - P. 97-110.

[25] 25. Mason M.R., Tannemaat M.R., Malessy M.J., Verhaagen J. Gene therapy for the peripheral nervous system: a strategy to repair the injured nerve // Curr. Gene Ther. - 2011. - Vol. 11, № 2. - P. 75-89.

[26] 26. McDonald C.L., Bandtlow C., Reindl M. Targeting the Nogo receptor complex in diseases of the central nervous system // Curr Med Chem. - 2011. - Vol. 18, № 2. - P. 234-244.

[27] 27. Moore D.L., Goldberg J.L. Multiple transcription factor families regulate axon growth and regeneration // Dev Neurobiol. - 2011. - Vol. 71. - № 12. - P. 1186-1211.

[28] 28. Morris R., Morgan B.S., Lewis T.M. et al. In vivo somatic delivery of plasmid DNA and retrograde transport to obtain cell-specific gene expression in the central nervous system // J. Neurochem. - 2004. - Vol. 90, № 6. - P. 1445-1452.

[29] 29. Nakajima H., Uchida K., Kobayashi S. et al. Rescue of rat anterior horn neurons after spinal cord injury by retrogradetransfection of adenovirus vector carrying brain-derived neurotrophic factor gene // J. Neurotrauma. - 2007. - Vol. 24, № 4. - P. 703-712.

[30] 30. Ohki E.C., Tilkins M.L., Ciccarone V.C., Price P.J. Improving the transfection efficiency of post-mitotic neurons // J. Neurosci Methods. - 2001. - Vol. 112, № 2. - P. 95-99.

[31] 31. Pizzi M.A., Crowe M.J. Transplantation of fibroblasts that overexpress matrix metalloproteinase-3 into the site of spinal cord injury in rats // J. Neurotrauma. - 2006. - Vol. 23, № 12. - P. 1750-1765.

[32] 32. Shi E., Jiang X., Kazui T. et al. Nonviral gene transfer of hepatocyte growth factor attenuates neurologic injury after spinal cord ischemia in rabbits // J. Thorac Cardiovasc Surg. - 2006. - Vol. 132, № 4. - P. 941-947.

[33] 33. Shibata M., Murray M., Tessler A. et al. Single injections of a DNA plasmid that contains the human Bcl-2 gene prevent loss and atrophy of distinct neuronal populations after spinal cord injury in adult rats // Neurorehabil Neural Repair. - 2000. - Vol. 14, № 4. - P. 319-330.

[34] 34. Takahashi K., Schwarz E., Ljubetic C. et al. DNA plasmid that codes for human Bcl-2 gene preserves axotomized Clarke's nucleus neurons and reduces atrophy after spinal cord hemisection in adult rats // J. Comp Neurol. - 1999. - Vol. 404, № 2. - P. 159-171.

[35] 35. Usachev Y.M., Khammanivong A., Campbell C. et al. Particle-mediated gene transfer to rat neurons in primary culture // Pflugers Arch. - 2000. - Vol. 439, № 6. - P. 730-738.

[36] 36. Washbourne P., McAllister A.K. Techniques for gene transfer into neurons // Curr. Opin. Neurobiol. - 2002. - Vol. 12, № 5. - P. 566-573.

[37] 37. Wiesenhofer B., Humpel C. Lipid-mediated gene transfer into primary neurons using FuGene: comparison to C6 glioma cells and primary glia // Exp. Neurol. - 2000. - Vol. 164. - № 1. - P. 38-44.

[38] 38. Xiang J.J., Tang J.Q., Zhu S.G. et al. IONP-PLL: a novel non-viral vector for efficient gene delivery // J. Gene Med. - 2003. - Vol. 5, № 9. - P. 803-817.

[39] 39. Yukawa Y., Lou J., Fukui N., Lenke L.G. Optimal treatment timing to attenuate neuronal apoptosis via Bcl-2 gene transfer in vitro and in vivo // J. Neurotrauma. - 2002. - Vol. 19, № 9. - P. 1091-1103.

RIGHTS & PERMISSIONS

Chelyshev Y.A., Мukhamedshina Y.O., Shaimardanova G.F., Nickolaev S.I.