CRISPR-Cas9-Based Technology and Its Relevance to Gene Editing in Parkinson’s Disease

Abstract

Parkinson’s disease (PD) and other chronic and debilitating neurodegenerative diseases (NDs) impose a substantial medical, emotional, and financial burden on individuals and society. The origin of PD is unknown due to a complex combination of hereditary and environmental risk factors. However, over the last several decades, a significant amount of available data from clinical and experimental studies has implicated neuroinflammation, oxidative stress, dysregulated protein degradation, and mitochondrial dysfunction as the primary causes of PD neurodegeneration. The new gene-editing techniques hold great promise for research and therapy of NDs, such as PD, for which there are currently no effective disease-modifying treatments. As a result, gene therapy may offer new treatment options, transforming our ability to treat this disease. We present a detailed overview of novel gene-editing delivery vehicles, which is essential for their successful implementation in both cutting-edge research and prospective therapeutics. Moreover, we review the most recent advancements in CRISPR-based applications and gene therapies for a better understanding of treating PD. We explore the benefits and drawbacks of using them for a range of gene-editing applications in the brain, emphasizing some fascinating possibilities.

Some Novel Therapies in Parkinson’s Disease: A Promising Path Forward or Not Yet? A Systematic Review of the Literature

“…Despite these challenges, the area of a gene cure for PD is rapidly advancing, with innovative gene editing technologies. Clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 offers new opportunities for precise gene modification and targeted correction of genetic mutations associated with PD [ 46 , 47 ]. By using CRISPR-Cas9, coupled to the DNA-methyltransferase 3A catalytic domain (DNMT3A), Kantor et al [ 48 ] decreased SNCA mRNA and protein in human induced pluripotent stem cell (hiPSC)-derived DNs from a PD patient with the triplication of the SNCA locus.…”

Development of Small Molecules Targeting α-Synuclein Aggregation: A Promising Strategy to Treat Parkinson’s Disease

“…Alternative gene therapies are based on the overexpression of growth and/or neuroprotective factors, such as glial cell-line derived neurotrophic factor, neurturin, artemin, persephin, vascular endothelial growth factor, or Nurr1 [ 218 , 219 , 220 , 221 ]. It has also been suggested that CRISPR/CAS9 technology could be used to correct genetic mutations associated with PD [ 222 ]. Other studied approaches were based on cellular transplantation.…”

Advances in graphene-based nanoplatforms and their application in Parkinson's disease

“…The pathological state is determined by the onset of cellular abnormalities ensuing propagation of its remarkable hallmarks, including pathological a-syn inclusions and chronic inflammation, which progresses with age. 8,9 The pathological processes and hallmarks of PD are shown in Fig. 1.…”