Myth Meets Reality
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Myth Meets Reality
Myth
In Celtic myth, Oisín (sometimes Ossian) was the Gælic warrior-bard of the 7th century who sought the land of youth – a magical island off the western coast of Ireland. Today Oisín Biotechnologies is working to make the myth a reality.
Reality
Oisín Biotechnologies' ground-breaking research and technology is demonstrating that the solution to mitigating the effects of age-related diseases is to address the damage created by the aging process itself. We invite you to see how.
The Approach
The Approach
Our First Target - Senescent Cells
When cells detect that they have been irreversibly damaged, they enter a non-dividing condition known as cell-cycle arrest, or senescence. It’s believed this occurs to prevent cells from going rogue and turning cancerous. Ideally, they should die by the process known as apoptosis, but as we age, more and more frequently they don’t. They become zombie cells – unable to kill themselves or resume normal function.
Senescent cells secrete molecules that cause inflammation in an effort to attract immune cells that would usually clear them. But for reasons that are not fully known, as we age, persistently senescent cells accumulate, leading to a vast number of age-related diseases.
Oisín is developing a highly precise, patent-pending, DNA-targeted intervention to clear these cells. As a recent study has shown, clearing senescent cells both reduces negative effects of aging pathologies and also extends median lifespan and survival.*
* Baker, Darren J., et al. "Naturally occurring p16Ink4a-positive cells shorten healthy lifespan." Nature 1038.16932 (2016)
Great Results
Great Results
Accomplishments to Date & the Future
There are two major challenges to clearing senescent cells using our approach.
First is to design and create the DNA construct that recognizes that a cell has become senescent, and then destroys it.
Second is to safely and efficiently deliver this construct into cells throughout the body.
Both goals have been achieved in our pioneering proof of concept experiments in 2016.
We’ve first demonstrated the ability to transduce cells both in vitro (cell culture) and in vivo (in aged mice). Then we showed that p16 positive senescent cells can be killed on demand in both in vitro and in vivo environments. Now we are embarked on experiments that will show improvements in both healthspan and lifespan in model organisms from mice to primates. And then, everything changes.
This video demonstrates the effectiveness of our SENSOlytic platform to kill cells with activated p16 pathway. Senescent cells strongly activate the p16 pathway, indicated by the expression of a green fluorescent protein reporter. We target these cells with a caspase-9 suicide gene triggered by the p16 promoter to which it is coupled. As the cells die via apoptosis, we can observe the green cells rapidly fading before disappearing completely.
This video demonstrates the effectiveness of our SENSOlytic platform to selectively kill a small number of p16-positive cells surrounded by many healthy, normal cells. All the cells in this video are labeled with a red fluorescent dye. Roughly 5% of the cells are p16 positive, as indicated by the green color. While all the cells take up the SENSOlytic gene therapy payload, the suicide gene is triggered only in the p16 positive cells and we can observe the green cells being rapidly killed while leaving the remaining red healthy cells untouched.
The Science
The Science
The Science of SENSOlytics®
Our proprietary technology gives persistently senescent cells a helping hand to “do the right thing." By providing an exogenous apoptotic gene, which is only transiently expressed in cells that already have the p16 gene active, we can precisely induce the senescent cell to commit suicide. Oisín has shown as much as an 80% reduction in senescent cells in cell culture and significant reductions of senescent cell burden in naturally aged mice.
*SENSOlytics® is an Oisín proprietary platform technology that enables precise targeting of a senescent cell based on the DNA expression of the cell, not on surface markers or other characteristics that might be shared with normal, undamaged cells.
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Contact us
Corporate Headquarters:
701 Fifth Ave, Suite 4200, Seattle, Washington 98104