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7.Samulski RJ, Muzyczka N. 2014. AAV-mediated gene therapy for research and therapeutic purposes. Annu Rev Virol 1:427–451.<br> | 7.Samulski RJ, Muzyczka N. 2014. AAV-mediated gene therapy for research and therapeutic purposes. Annu Rev Virol 1:427–451.<br> | ||
8.Zhou Y, Zhou G, Tian C, Jiang W, Jin L, Zhang C, et al. Exosome-mediated small RNA delivery for gene therapy. Wiley Interdiscip Rev RNA (2016) 7(6):758–71.10.1002/wrna.1363<br> | 8.Zhou Y, Zhou G, Tian C, Jiang W, Jin L, Zhang C, et al. Exosome-mediated small RNA delivery for gene therapy. Wiley Interdiscip Rev RNA (2016) 7(6):758–71.10.1002/wrna.1363<br> | ||
− | 9.Liu Y, Li D, Liu Z, et al. Targeted exosome-mediated delivery of opioid receptor Mu siRNA for the treatment of morphine relapse. Sci Rep. 2015;5:17543 | + | 9.Liu Y, Li D, Liu Z, et al. Targeted exosome-mediated delivery of opioid receptor Mu siRNA for the treatment of morphine relapse. Sci Rep. 2015;5:17543 |
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Revision as of 16:51, 17 October 2018
Background
In the past years, The focus of our team is mainly on the construction and utility of the exosomes in different fields. With RVG modified exosomes, we successfully realized the transportation of specific molecules into the brain. (NJU-China:2015)
Following the exploration in the brain, the neurons are a typical kind of cells in our body where the mRNA could exist and produce certain proteins far from the soma of the cell. The neurites, for example, contain certain mRNAs to refresh local proteins. In some cases when the RNA transportation and localization system breaks down, some disease could then occur. If we would like to find a cure for these diseases and study the physiological and pathological mechanism of mRNA transportation and local translation, some specific targeting elements within the cells should be applied, the 3’-UTR (un-translated region) from β-Actin is one of the candidates. However, 3’-UTR is normally longer in length. With some literature review, we learned that TBEV (tick-borne encephalitis virus) 5’-UTR is capable of bringing the virus genome to the dendrite. Since the viral element is rather small, and the transportation efficiency is expected to be higher, we assume that this could be an excellent mRNA transportation element in use. However, the cytotoxic and transportation efficiency of the TBEV 5’-UTR remain to be tested.
Meanwhile, when carrying out the experiments we found that TBEV 5’-UTR has a rather low concentration in exosomes, so we began searching for other packaging tools. Thanks to the visit to a biological company, we learned that the AAV (adeno-associated virus) virus has many advantages such as low immunogenicity and long persistence in the cell. Besides, the virus has brighter prospect and better policy support in the treatment of neuron diseases. Other physiological and pathological significance also inspires us to carry out the exploration.
References
1.Ethan J. Greenblatt and Allan C. Spradling, Fragile X mental retardation 1 gene enhances the translation of large autism-related proteins, Science, 361(6403), 709-712
2.Bassell G. J., Zhang H., Byrd A. L., Femino A. M., Singer R. H., Taneja K. L., et al. . (1998). Sorting of beta-actin mRNA and protein to neurites and growth cones in culture. J. Neurosci. 18, 251–265.
3.Glock C., Heumüller M., Schuman E. M. (2017). mRNA transport and local translation in neurons. Curr. Opin. Neurobiol. 45, 169–177.
4.Hirano M., Muto M., Sakai M., Kondo H., Kobayashi S., Kariwa H., Yoshii K. Dendritic transport of tick-borne flavivirus RNA by neuronal granules affects development of neurological disease. Proc. Natl. Acad. Sci. USA. 2017;114:9960–9965
5.Uutela M, Lindholm J, Louhivuori V, Wei H, Louhivuori LM, Pertovaara A, Akerman K, Castrén E, Castrén ML. (2012) Reduction of BDNF expression in Fmr1 knockout mice worsens cognitive deficits but improves hyperactivity and sensorimotor deficits. Genes Brain Behav 11:513–523.
6.Giovanni Neri and Pietro Chiurani, X-linked Mental Retardation, 1999, Advances in Genetics, VoI. 41
7.Samulski RJ, Muzyczka N. 2014. AAV-mediated gene therapy for research and therapeutic purposes. Annu Rev Virol 1:427–451.
8.Zhou Y, Zhou G, Tian C, Jiang W, Jin L, Zhang C, et al. Exosome-mediated small RNA delivery for gene therapy. Wiley Interdiscip Rev RNA (2016) 7(6):758–71.10.1002/wrna.1363
9.Liu Y, Li D, Liu Z, et al. Targeted exosome-mediated delivery of opioid receptor Mu siRNA for the treatment of morphine relapse. Sci Rep. 2015;5:17543