Assessment of CRISPRa-mediated overexpression in an Parkinson's disease model.

INTRODUCTION

Parkinson's disease (PD) presents a significant challenge in medical science, as current treatments are limited to symptom management and often carry significant side effects. Our study introduces an innovative approach to evaluate the effects of overexpression mediated by CRISPRa in an model of Parkinson's disease. The expression of can have neuroprotective effects, being related to the modulation of neuroinflammation and pathways associated with cell survival, differentiation, and growth.

METHODS

We have developed a targeted delivery system using a magnetite nanostructured vehicle for the efficient transport of genetic material. This system has resulted in a substantial increase, up to 200-fold) in expression in an model of Parkinson's disease using a mixed primary culture of astrocytes, neurons, and microglia.

RESULTS AND DISCUSSION

The delivery system exhibits significant endosomal escape of more than 56%, crucial for the effective delivery and activation of the genetic material within cells. The increased expression correlates with a notable reduction in MAO-B complex activity, reaching basal values of 14.8 μU/μg of protein, and a reduction in reactive oxygen species. Additionally, there is up to a 34.6% increase in cell viability in an Parkinson's disease model treated with the neurotoxin MPTP. Our study shows that increasing expression can remediate some of the cellular symptoms associated with Parkinson's disease in an model of the disease using a novel nanostructured delivery system.