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Funded Studies

Pre-clinical Knockout Models of Parkinson's Disease

The objective of this project will be to use Sigma’s novel CompoZr (TM)  ZFN technology to genetically engineer five distinct pre-clinical models in which genes implicated in Parkinson’s disease have been removed from the genome, or ‘knocked out.’
These models will be used as tools to better understand the genetic basis of Parkinson’s disease and will serve as a platform to develop new therapeutics targeting the condition.
Project Description:
While it clear that there are many genes implicated in Parkinson’s disease, this study will focus on five key genes that are believed to have a major role, either individually or in concert. They are, in no particular order: Parkin, PINK1, DJ-1, LRRK2, and alpha-synuclein.
Using publicly available DNA sequence, a series of reagents called Zinc Finger Nucleases (ZFN) will be created that specifically target each gene. Through standard scientific methodologies, these ZFN reagents will be injected into early stage pre-clinical model embryos, causing a single gene-specific mutation and resulting in disruption of the targeted gene.
These treated early-stage embryos are than incubated, resulting, after a gestation period, in models lacking the targeted genes. Models lacking the genes in question are considered “knockouts” for the gene.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
Pre-clinical models of Parkinson’s disease in existence today have been less than ideal in their ability to faithfully approximate the complex behavioral aspects of the disease. It is believed that our knockout models will more faithfully reproduce the Parkinson’s condition, allowing us to reach more predictive conclusions in treating the human disease.
Anticipated Outcome:
It is expected that the models produced as a result of this project will exhibit signs of Parkinson’s  to varying degrees at the molecular, biochemical, physiological, and behavioral levels. Because a different gene will have been systematically ‘knocked out’ in each of the five models, the scientific community will be able make improved hypotheses regarding the causative effect that each gene exerts on the disease condition. This in turn will lead to a better understanding of the targets against which to develop novel therapuetics.


  • Edward J. Weinstein, PhD

    St. Louis, MO United States

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