| Autor: |
Narváez-Pérez, Luis Fernando, Paz-Bermúdez, Francisco, Avalos-Fuentes, José Arturo, Campos-Romo, Aurelio, Florán-Garduño, Benjamín, Segovia, José |
| Zdroj: |
Gene Therapy; January 2024, Vol. 31 Issue: 1-2 p31-44, 14p |
| Abstrakt: |
Parkinson`s disease (PD) is the second most prevalent neurodegenerative disease, and different gene therapy strategies have been used as experimental treatments. As a proof-of-concept for the treatment of PD, we used SAM, a CRISPR gene activation system, to activate the endogenous tyrosine hydroxylase gene (th) of astrocytes to produce dopamine (DA) in the striatumof 6-OHDA-lesioned rats. Potential sgRNAs within the rat thpromoter region were tested, and the expression of the Th protein was determined in the C6 glial cell line. Employing pseudo-lentivirus, the SAM complex and the selected sgRNA were transferred into cultures of rat astrocytes, and gene expression and Th protein synthesis were ascertained; furthermore, DA release into the culture medium was determined by HPLC. The DA-producing astrocytes were implanted into the striatumof 6-OHDA hemiparkinsonian rats. We observed motor behavior improvement in the lesioned rats that received DA-astrocytes compared to lesioned rats receiving astrocytes that did not produce DA. Our data indicate that the SAM-induced expression of the astrocyte´s endogenous thgene can generate DA-producing astrocytes that effectively reduce the motor asymmetry induced by the lesion. |
| Databáze: |
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