THE SCIENCE OF CELLULAR RENEWAL
The cellular reprogramming evolution
ERA™ and iPSC represent two ends of the cellular reprogramming continuum. Both technologies use carefully formulated mRNA cocktails of transcription factors – specific proteins like Myc, Oct3/4, Sox2 and Klf4 – that turn a gene on or off by controlling the rate of transcription of genetic information from DNA to messenger RNA. This information controls the cell’s function.
With ERA™, a cell’s exposure to both the dosing and timing of transcription factors is carefully controlled and more limited than with iPSC. The goal is to maintain cellular identity, but restore cell effectiveness by “turning back the clock” on the epigenome, which regulates how a cell functions and records cellular age.
Over their lifespan, cells accumulate defects in the epigenome that translate to irregularities in gene expression and extracellular signaling, and can ultimately result in cell and tissue dysfunction. Imagine an audio cassette. If the tape gets mangled, unwound or broken, it distorts the sound. To combat this and restore cells to youthful function, our transformative ERA™ therapy harnesses the power of stem cell reprogramming, effectively rejuvenating without disturbing cellular identity.
With iPSC, cells are exposed to a sufficient dosage of the factors for a long enough period of time to eliminate the cells’ identities. This effectively converts somatic cells that have a designated function, such as lung cells or skin cells, into pluripotent stem cells that have no assigned function in the body and can differentiate into any type of cell.
Turn’s mRNA-based ERA™ Platform is safe and fast
Turn Biotechnologies’ proprietary ERA™ Platform uses mRNA to deliver transcription factors to the epigenome. The platform is safe, fast, efficient and tunable.
Turn’s ERA Platform enables us to carefully control the time, duration and dosage of transcription factors to optimize the mRNA cocktail for each indication. For example, we can add or subtract specific factors, depending on the benefit they provide with specific tissue.
Then we can control reprogramming, moving the epigenome to a more youthful state one step at a time, by carefully pulsing the cell with the transcription factors. As the animation below shows, each pulse drives the epigenome to a more vigorous state, protecting the patient while steadily restoring cell functionality.
Our AN™ technology extends the power of ERA™
As Turn explores new therapies, we have found the use of quiescent stem cells can significantly help to repair or replace specific types of damaged tissue. But great care is needed to preserve the quiescence of these stem cells to ensure they remain poised in anticipation of activation, proliferation and differentiation.
In these cases, we deploy Turn’s own Artificial Niche (AN) technology to protect the stem cells. AN technology combines stem cell biology with biomolecular materials engineering and microfabrication technologies to generate novel cell culture platforms that mimic crucial biochemical or structural aspects of the niche.
We have found that muscle stem cells (MuSCs) maintained in an AN microenvironment show enhanced potential for engraftment, tissue regeneration and self-renewal after transplantation.
When AN is deployed in combination with our ERA technology in aged murine models to restore aged stem cells, we see increased potency and our studies show that aged MuSCs treated with a combination therapy, fully regenerate age-related muscle dysfunctions (such as muscle weakness), similarly to MuSCs transplanted from young donors.
Our approach for maintaining quiescence may also be applicable to stem cells isolated from other tissues. The most promising candidates are tissues where quiescence is a necessary condition to maintain stem cell functions, such as the hematopoietic, liver, brain compartments, but also certain mesenchymal stem cells across different tissues, and most likely the hair follicle (where quiescence plays a crucial role in its niche cycle).
Delivery System
Turn Bio’s novel eTurna Platform™ overcomes the biggest challenge facing cell therapy researchers worldwide and was developed for the next generation of precision medicine. It can safely and effectively deliver a variety of cargoes requiring different routes of administration and be finely tuned and targeted to specific tissue and cells. Traditional lipid carriers, which were designed primarily to deliver vaccines, have proven inadequate for many localized therapy applications because of their instability, poor bioavailability, poor solubility and poor absorption in the body. These problems threaten delivery challenges and potentially create severe adverse effects for patients.
Turn Bio’s nanostructure carrier sidesteps these issues, can be adapted for individual therapies and tuned for use through different routes of administration. The platform allows for rapid development of unique formulations that can precisely steer the right mRNA or other cargo to the right organs, tissues and cell types.
While the delivery technology was developed to deliver Turn Bio’s mRNA-based gene therapies, it can also carry other companies’ therapeutic cargoes through collaborations that will unlock the potential of emerging therapeutics while fueling the eTurna delivery platform’s expansion into a variety of markets.
PUBLISHED RESEARCH
Turn Biotechnologies’ science has been discussed in a number of scientific articles and presentations:
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