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 |
|---|---|---|---|---|---|---|---|
| Ophthalmology | mogrify | mogrify | mogrify | partner | partner | ||
| Immunology (& hematology) |
mogrify | mogrify | mogrify | mogrify | partner | partner | |
| Collaborations (Pancreatic, Lung, Immune & Others) |
mogrify | mogrify | mogrify | partner | partner | partner | partner |
| mogrify | Mogrify Progress | partner | Expect to Partner |
Featured
RESOURCES
Approximately 1 in 2,000 people worldwide are affected by inherited retinopathies but few treatment options are available for retinal degeneration. There is also no cure for glaucoma, which affects 60 million people worldwide and is caused by degeneration of retinal ganglion cells (RGCs) and their axon bundles. The FDA’s 2017 approval of LUXTURNA to treat inherited retinal degeneration caused by biallelic mutations in RPE65 has established viral vectors as a viable clinical therapy to monogenic retinal disease. Furthermore, advances in pluripotent stem cell techniques have enabled retinal pigment epithelium (RPE) to reach clinical trials as a cell therapy for treating age-related macular degeneration (AMD).
Current treatment of type 1 diabetes mellitus (T1DM) depends on regular subcutaneous injections of exogenous insulin. Unfortunately, insulin therapy is associated with patient compliance issues and life-threatening hypoglycaemic events. Alternatively, recent convergences of biomaterial and regenerative medicine advances suggest transplantation of stem cell-derived beta cells as an “off-the-shelf” cell therapy treatment approach to T1DM, potentially providing long-term therapeutic benefits to patients, with minimal adverse effects.
This review published in Cell & Gene Therapy Insights discusses the current challenges for autologous and allogeneic adoptive cellular therapies (ACT) and how big dataset analysis is opening paths to overcome resistance and enhance the efficacy of ACT.