The latest crowdfunded research project undertaken by the SENS Research Foundation involves using the genetically engineered maximally modifiable mouse lineage in order to demonstrate the ability to copy a version of the ATP8 mitochondrial gene into the cell nucleus, a process known as allotopic expression, and thus prevent mutational damage to this gene from degrading mitochondrial function. This is a modest step on the road towards bringing this class of genetic engineering project to the point of readiness for commercial development, when a biotech startup company could be created to carry it forward.
In just a few weeks of crowdfunding, the project has already hit the initial funding goal of $50,000. There are still stretch goals to reach, however - so if you want to see more work on preventing the mitochondrial contribution to aging, then join in and help.
Mitochondria are the power plants of the cell, every cell containing a herd of these organelles, descendants of ancient symbiotic bacteria. They bear a remnant of the original bacterial DNA, and that is where the problems start. This DNA encodes thirteen proteins vital to the operation of mitochondria. Unfortunately, this genome is poorly protected, poorly repaired, and vulnerable to the oxidative molecules generated by mitochondria as a side-effect of their duties in the cell. Some forms of damage, such as major deletions, can cause mitochondria to become both dysfunctional and more competitive, in replication and resistance to quality control mechanisms, than their undamaged peers. The cell is quickly taken over by broken mitochondria, and becomes broken itself, exporting oxidative molecules into the surrounding tissue. This contributes to the aging process.
If, however, copies of these mitochondrial genes are placed into the cell nucleus, then DNA damage in the mitochondria will not affect their function. The necessary proteins will still be manufactured, delivered, and used. This has been demonstrated for the ND4 gene in recent years, that development program conducted by Gensight Biologics, and the SENS Research Foundation team have achieved allotopic expression of ATP6 and ATP8 in cell studies. More and faster progress is needed, however, to move this work into animal models, and then towards human studies.
The MitoMouse Project Smashes its Initial Fundraising Goal!
Wonderful news, the MitoMouse project has successfully reached its initial $50,000 goal and is well on the way towards the first stretch goal! This now means the project will launch at the lab and the MitoMouse strain will be created. The next step for this ambitious project is to actually create progeny from the SickMice and MitoMice in order to have an effective model to test the mitochondrial repair approach, which has already been shown to work in cells, in living animals. If successful it would be vindication for mitochondrial repair therapy and move the therapy closer to translation to humans.
MitoMouse: SENS Transgenic Mouse Project
Mice of the C57/BL6MT-FVB strain (let's call them "SickMice") have a mitochondrial gene defect (a mutation in the mitochondrial ATP8 gene) and exhibit several age-related symptoms including lower fertility, arthritis, type II diabetes, and neurological impairments. Since mitochondria are only inherited from the mother, cross-breeding female SickMice with male mice from other models will result in the same mitochondrial dysfunction.
We will use the maximally modifiable model to create a new transgenic mouse (the "allotopic ATP8 transgenic mouse - Mitomouse"). This mouse will have the ATP8 gene that is important for mitochondrial function 'hidden' in the cell nucleus and thus capable of being passed on to offspring irrespective of gender.
Our hypothesis is that both male and female offspring from SickMice crossed with MitoMice will result in rescued mitochondrial function. This would prove the viability of the MitoSENS strategy by showing that functional backup copies of mitochondrial DNA genes in the nucleus can replace their mutated counterparts in live animals.
View the full article at FightAging
