Mitochondrial Makeover: Replacing Old Power Sources with New

The Problem

Aging creates an accumulation of mutations in the DNA of our mitochondria, the organelles that create our energy supply on a molecular level. This impacts and impairs their ability to function correctly and creates a myriad of energy issues as we age. 

The Goal

The team is creating a drive to implant new genes more aggressively, like a sped-up evolutionary track, through mitochondria that have been engineered with an enzyme capable of destroying all current mitochondrial DNA in a cell. These new mitochondria will replace all the mutated and aged mitochondria with healthy, functional mitochondria entirely. 

The Status

The first hurdle was overcome when the team developed a way to keep new mitochondria within the cells – which had never been previously accomplished.  They are working to optimize the percentage of surviving mitochondria before fully engineering the more aggressive strains for injection.


A Gene Drive Strategy for Mitochondrial Mutations

The Boominathan lab is in the preliminary stages of developing a gene drive solution to mitochondrial mutations. Gene drives are a biotechnology that mimics naturally-occurring genetic elements that enhance their own propagation through a population at the expense of other genes in the genome, independently of natural selection mechanisms. The strategy is to engineer mitochondria with wild-type genomes except for a restriction enzyme that would cleave restriction sites in native mitochondrial genomes, destroying them and replacing them over the course of cycles of mitochondrial fusion and fission.

The targeted restriction site would be engineered out of therapeutic mitochondria to allow them to escape its effects. This would leave the cell with fully functional mitochondria without reference to the initial state of the cell’s mitochondrial genomes. The approach would be repeatable by alternating the targeted restriction site for each round of treatment.

The initial benchmark achieved is the incorporation of mitochondria into cells in culture persisting for extended periods. Previous reports in vitro and in vivo mitochondrial transplantation have found that the transplanted mitochondria are only detectable for periods less than two weeks. The Boominathan lab’s new protocol enables small numbers of transplanted mitochondria to persist for months, but even very few persistent gene drive-enabled mitochondria would be sufficient to progressively repopulate the host cells.


Team Members

Please visit the Work With Us page to learn about available positions.

amutha-boominathan

Amutha Boominathan, PhD

Principal Investigator


Funding

Annual Budget
225,000 USD

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