478725 Pentablock Copolymer Mediated Crispr/Cas9 Delivery Strategies in Astrocyte Type Cells Transdifferentiated from Mesenchymal Stem Cells for in Vitro Gene Therapy

Monday, November 14, 2016
Grand Ballroom B (Hilton San Francisco Union Square)
Pratish Adhikari, Iowa State University, Ames, IA

Parkinson's and Alzheimer’s are the most common neurodegenerative diseases in United States. Currently, these neurodegenerative disease can’t be cured, and medications are only used to improve symptoms and treat patients. The morphological hallmarks of inflammatory and neurodegenerative disease are caused by enlargement of astrocytes and accumulation of macrophages. In recent literature, production of granulocyte-macrophage-colony–stimulating factor (GM-CSF) by astrocytes has been suggested to contribute to the macrophage response. GM-CSF secreted by astrocyte has shown to enhance the local inflammatory response to central nervous system injury and to activate macrophage aggregation. Also, increasing evidence suggests that α-synuclein aggregates can activate astrocyte cells to induce these neruroinflammation. In this study, amphilic pentablock copolymer was used to efficiently deliver gene editing tool of CRISPR/Cas9. CRISPR/Cas9 was used to efficiently target GMC-SF gene to decrease the gene’s effects on Astrocyte that causes astroctytosis, which is a hallmark of various neurological injuries an in inflammatory processes. Polymer transfected with CRISPR/Cas9 on GDNF derived Astrocytes showed lower GM-CSF concentration compared with just CRISPR/Cas9 delivered. Additionaly, it is shown that primary astrocytes loaded with α-synuclein secretes higher concentration of GM-CSF compared with cells that was treated with CRISPR/Cas9. With this study, we were able to show that the amphiphilic polymer is effective for delivering CRISPR-Cas9 gene editing tool to treat genetic diseases.

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