EpiMOGRIFY PLATFORM
Systematically identify the epigenetically-predicted factors required
to drive and maintain cell identity.
EpiMOGRIFY is an extension of the Company’s proprietary direct cellular conversion technology, MOGRIFY®, that enables the identification of the optimal culture conditions required to maintain cells and support conversions in chemically defined media. This can be applied in cGMP manufacture and enhances directed differentiation or cell conversion to support the development of scalable off-the-shelf therapies for diseases with a high unmet clinical need.
EpiMOGRIFY combines gene-regulatory information with a model of a cell’s epigenetic landscape and leverages changes in the level of DNA-histone methylation (H3K4me3 modifications). The platform utilizes data from more than 100 human cell/tissue types (available via the ENCODE and Epigenome Roadmap consortia) to accurately define culture conditions that can maintain the cell identity or induce cell conversion.
The predictive power of EpiMOGRIFY has been validated in two ways: cell maintenance and differentiation. EpiMOGRIFY-predicted factors are able to maintain astrocytes and cardiomyocytes in vitro in chemically defined media, and promote the generation of astrocytes and cardiomyocytes from neural progenitors and embryonic stem cells, respectively. In both cell maintenance and differentiation, EpiMOGRIFY defined conditions performed as well or better in all cases when compared to existing undefined conditions, significantly increasing cell growth and survival, as well as resulting in a higher differentiation efficiency.
Step 1 H3K4me3 histone modification sequencing using ChIP-seq (chromatin-immunoprecipitation)
Step 2 Cell identity gene identification using ChIP-seq data (ENCODE)
Step 3 Key receptor identification, using the same “engine” as MOGRIFY® (considers both direct and indirect effects)
Step 4 Ligand identification for both paracrine & autocrine ligands
Patent pending on the EpiMOGRIFY platform, validated conversion and maintenance of specific cell types. Images adapted from Kamaraj et al., EpiMogrify Models H3K4me3 Data to Identify Signaling Molecules that Improve Cell Fate Control and Maintenance. Cell Systems (2020).
Applying Mogrify and EpiMogrify
To ENHANCE
Efficacy
- Enhances existing stem-cell forward reprogramming methods.
- Bypasses development pathways altogether, affecting direct transdifferentiation between a mature cell type to another.
Safety
- Produces mature cells to avoid the tumorigenicity- and immunogenicity-associated characteristics of pluripotent stem cells.
- Queries FANTOM5 and other proprietary data sources to improve prediction quality, prediction accuracy and cell conversion efficacy.
Scalability
- Produces any target cell type from any source cell type.
- Identifies the optimal culture conditions required to maintain and support the conversion of cells in chemically defined media.
- Capacity to identify small molecules known to affect the expression of the key Mogrify predicted transcription factors, avoiding the need for their transduction, and offering greater potential as an in vivo reprogramming therapy.
Our
PIPELINE
| AREA | Sample Acquisition | Bioinformatics | In vitro PoC | In vivo PoC | IND | Clinical | Marketing |
|---|---|---|---|---|---|---|---|
| Immunotherapy (Oncology) |
mogrify | mogrify | mogrify | mogrify | partner | partner | |
| Ophthalmology (Retinal) |
mogrify | mogrify | mogrify | partner | partner | ||
| Collaborations (Pulmonary, Metabolic & Others) |
mogrify | mogrify | mogrify | partner | partner | partner | partner |
| mogrify | Mogrify Progress | partner | Expect to Partner |
Featured
RESOURCES
Over the last two decades, scientists have sequenced the genome and epigenome of all known cell types in the human body, in addition to mapping hundreds of possible protein-protein interactions. The availability of biological data at this resolution and scale has enabled the development of computational tools capable of addressing the challenges associated with the development of scalable cell therapies.
Cell therapy is a powerful strategy to treat and cure diseases that have been untreatable to date. For many diseases, including heart disease, diabetes, and liver failure, cell replacement remains the only option for curative therapy. However, the development of cell therapies is tightly linked to our ability to culture cells in artificial environments outside of the body, i.e., in vitro conditions. In our bodies, cells live in highly regulated and specialized microenvironments, also known as niches.
In the delivery of scalable cell therapies, there is a fundamental need to derive viable cells in vitro. In addition to developing cell cultures that mimic in vivo conditions for the maintenance of target cell types, cells need to acquire and develop specific therapeutic characteristics. How can epigenetics and innovative computational approaches be implemented to drive cell identity and scalability in cell therapy?
The webinar features panelists Dr. Zoe Hewitt (UK Regenerative Medicine Platform), Dr. Owen Rackham (Duke-NUS Medical School) and Dr. Rodrigo Santos (Mogrify).