Objective/Rationale:
LRRK2 is a gene that is has been implicated in Parkinson’s disease. LRRK2 is a large cDNA of approximately 7.6 kb that precludes it from being expressed in viral vectors such as recombinant Adeno-associated virus and lentiviral vectors. In order to study, LRRK2 function and its dominant negative mutations one needs a viral vector that permits expression of LRRK2. Helper Dependent Adenovirus which can package up to 37 kb of cDNA are an ideal viral vector system for LRRK2 expression. The goal of this project is to design a HdAd LRRK2 expression vector that can be used by all Parkinson disease researchers.
Project Description:
This project will comprise a coordinated effort between MJFF, my lab, other experts in the field and contract research organizations. Ultimately, my lab will work to identify the elements that can be incorporated to ultimately generate the optimal Helper-dependent Adenoviral vector to express LRRK2 in in vivo studies.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
Currently, researchers in the Parkinson’s disease field are limited in their ability to study LRRK2 function in pre-clinical models due to the inability to express LRRK2 with viral vectors. By creating a HdAd viral vector that expresses LRRK2 and its dominant negatives this will allow researchers to use this viral vector to help elucidate the mechanisms of LRRK2 function in vivo and design relevant therapeutics.
Anticipated Outcome:
An optimal viral vector that expresses LRRK2 neurospecifically will be generated that all Parkinson disease researchers can use in their research projects.