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Review
. 2021 May 28;9(6):613.
doi: 10.3390/biomedicines9060613.

Planet of the AAVs: The Spinal Cord Injury Episode

Katerina Stepankova  1   2 , Pavla Jendelova  1   2 , Lucia Machova Urdzikova  1   2
Affiliations
Review

Planet of the AAVs: The Spinal Cord Injury Episode

Katerina Stepankova et al. Biomedicines. .

Abstract

The spinal cord injury (SCI) is a medical and life-disrupting condition with devastating consequences for the physical, social, and professional welfare of patients, and there is no adequate treatment for it. At the same time, gene therapy has been studied as a promising approach for the treatment of neurological and neurodegenerative disorders by delivering remedial genes to the central nervous system (CNS), of which the spinal cord is a part. For gene therapy, multiple vectors have been introduced, including integrating lentiviral vectors and non-integrating adeno-associated virus (AAV) vectors. AAV vectors are a promising system for transgene delivery into the CNS due to their safety profile as well as long-term gene expression. Gene therapy mediated by AAV vectors shows potential for treating SCI by delivering certain genetic information to specific cell types. This review has focused on a potential treatment of SCI by gene therapy using AAV vectors.

Keywords: AAV vector; adeno-associated virus; gene therapy; spinal cord injury.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Spinal cord injury pathology. The regeneration following traumatic spinal cord injury (SCI) fails especially due to: (1) glial scar formation and changed extracellular matrix (ECM) environment caused by secretion of tenascin, chondroitin sulfate proteoglycans (CSPGs) such as brevican, phosphacan, neurocan, versican, and NG2 proteoglycans. All of these molecules lead to the activation of Rho-ROCK signaling pathway inhibiting regeneration; (2) Neurotransmitter imbalance, excitotoxicity, and free radicals release caused by overstimulation of cells; (3) inhibitory molecules associated with the ECM and those associated with myelin such as MAG, OMgp, Nogo-A released after myelin disintegration (Created with BioRender.com).
Figure 2
Figure 2
Gene therapy applications shown in preclinical SCI models. AAV vectors can express (1) pro-regenerative factors, (2) circuit-modifying factors, (3) repressors for inhibitory factors, and (4) matrix/glial scar-modifying factors (Created with BioRender.com).
Figure 3
Figure 3
Possible routes of AAV vector administration into the spinal cord: (1) intraparenchymal, (2) intraneural, (3) intrathecal, (4) intramuscular, and (5) intravenous AAV delivery (Created with BioRender.com).
Figure 4
Figure 4
Schematic representation of connections between pro-regenerative factors and transcription factors (TFs) targeted in AAV-mediated gene therapy. Pro-regenerative factors and TFs mentioned in the text above the figure are marked in colors (Created with BioRender.com).
Figure 5
Figure 5
Schematic representation of experimentally inactivated targets mentioned in the text above. Inhibitors and TFs due to which CNS effort to regenerate fails are marked in red (Created with BioRender.com).
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References

    1. McDonald J.W., Sadowsky C. Spinal-Cord Injury. Lancet Lond. Engl. 2002;359:417–425. doi: 10.1016/S0140-6736(02)07603-1. - DOI - PubMed
    1. Eckert M.J., Martin M.J. Trauma: Spinal Cord Injury. Surg. Clin. N. Am. 2017;97:1031–1045. doi: 10.1016/j.suc.2017.06.008. - DOI - PubMed
    1. Cappella M., Ciotti C., Cohen-Tannoudji M., Biferi M.G. Gene Therapy for ALS-A Perspective. Int. J. Mol. Sci. 2019;20:4388. doi: 10.3390/ijms20184388. - DOI - PMC - PubMed
    1. Tuszynski M.H., Yang J.H., Barba D., Hoi-Sang U., Bakay R.A.E., Pay M.M., Masliah E., Conner J.M., Kobalka P., Roy S., et al. Nerve Growth Factor Gene Therapy: Activation of Neuronal Responses in Alzheimer Disease. JAMA Neurol. 2015;72:1139–1147. doi: 10.1001/jamaneurol.2015.1807. - DOI - PMC - PubMed
    1. Hara H., Monsonego A., Yuasa K., Adachi K., Xiao X., Takeda S., Takahashi K., Weiner H.L., Tabira T. Development of a Safe Oral Abeta Vaccine Using Recombinant Adeno-Associated Virus Vector for Alzheimer’s Disease. J. Alzheimers Dis. JAD. 2004;6:483–488. doi: 10.3233/JAD-2004-6504. - DOI - PubMed

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