A big thank you to everyone for helping us hit our goal so quickly! Please check out the campaign updates tab to learn about our stretch goals for hitting $45,000 and $60,000.

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Each cell in the body is dependent on the efficient generation of cellular energy by mitochondria to stay alive. Critical to this process are genes encoded within the mitochondrial genome. Over time however, mutations in these genes occur as a result of constant exposure to reactive oxygen species produced by oxidative phosphorylation, the mitochondrial energy generation process. Unlike genes within the nucleus, mitochondria lack an efficient system to repair damaged DNA. This leads to accumulated mutations, resulting in mitochondrial defects and an increase in oxidative stress throughout the body. Closely correlated with this is the observation that organisms which age more slowly also consistently display lower rates of mitochondrial free radical damage. Thus, reversing and/or preventing damage to mitochondrial DNA may be a key factor in slowing the aging process.

At the SENS Research Foundation, we are in the early stages of creating an innovative system to repair these mitochondrial mutations. If this project is successful we will have demonstrated, for the first time, a mechanism that can provide your cells with a modified backup copy of the entire mitochondrial genome. This genome would then reside within the protective confines of the cell’s nucleus, thereby mitigating damage to the mitochondrial genome. In fact, during the long course of evolution, this gradual transfer of genetic information into the nucleus has already occurred with the majority of mitochondrial genome, leaving behind a mere 13 protein coding genes within the mitochondria. Demonstrating the effectiveness of this technology would be a major milestone in the prevention and reversal of aging in the human body.

Edward James Olmos describes the SENS Mitochondrial Repair Plan

We are also developing a unique method for guiding the products of these nuclear encoded mitochondrial genes back into the mitochondria, where they can then properly function. Over the last decade, engineering this last step has been the major bottleneck in achieving effective results. In our novel system, the mRNA from an engineered mitochondrial gene is guided back to the mitochondrial surface, where it is then translated into a protein by the organelle’s co-translational import system (see figure below). Once imported, it is then incorporated into the correct location within the inner mitochondrial membrane.

Our precise targeting is achieved by adding a specific sequence “tag” to both ends of the mRNA. These tags then serve to guide the information containing mRNA molecule to the mitochondrial surface. Our prior research indicates that our system of tagging yields a significantly higher efficiency of import to mitochondria than any previously published research.

Visualization of engineered ATP8 expressed in mutant cells

Successfully completing this project will mean that we have developed a groundbreaking method that will provide us with the capability to safeguard the mitochondrial genome by creating a backup copy in the nuclear genome. The overall goal will be to test this improved targeting technology so that it can be optimally refined for use in rescuing mutated mitochondrial DNA, and thus prevent and cure what may be one of the major causes of cellular aging.

In our current research, we are using cells derived from a patient suffering from a rare mitochondrial disease, that are null for the mitochondrial ATP8 gene (i.e., the ATP8 protein is completely absent). We have inserted our improved versions of the ATP8 gene, equipped with our specialized mitochondrial tagging system, into the nuclear genome. Inserting it into the nuclear genome helps to protect the gene from oxidative damage, while our tagging system will help guide the functional protein into the mitochondria where it is needed.

We need your support at this critical juncture of the MitoSENS project. The MitoSENS team has already demonstrated the rescue of cells containing mitochondrial mutations, and has recently generated highly promising preliminary data showing the rescue of the complete loss of a mitochondrial gene. Our next steps will focus on improving the effectiveness of the targeting system, so that we can repeat our success with one mitochondrial gene to all thirteen. We will then transition this work into animal models of mitochondrial dysfunction. This would be a crucial step in what may be the development of an eventual cure for aging and aging related diseases.

We have a talented team of highly trained mitochondrial biologists working on MitoSENS. Right now the rate-limiting factor is the cost of the expensive reagents that we use for these experiments. Increasing our funding with this campaign will allow us to double the pace of our research and bring results to the public that much faster. We have made preliminary progress on rescuing function with a second gene, ATP6, and your support will help us perfect our targeting of both ATP8 and ATP6. This requires more cells, more viruses, and many new synthetic gene sequences. Specifically, we will spend your generous donations on cell culture reagents, oxygen consumption measurements, virus production, quantitative reverse transcription PCR, DNA synthesis services, and publication of our results in a peer-reviewed journal.

Your support will help take us there.

Thank You.