direct cellular conversion

What makes Mogrify Unique

Mogrify® is a proprietary direct cellular conversion technology, which addresses the speed and efficiency of cell conversions through the identification of key regulatory switches, such as transcription factors, for the development of scalable cell therapies.

With the capacity to convert any human cell type into any other, Mogrify represents a unique opportunity to transform the development of ex vivo cell therapies or in vivo reprogramming therapies for diseases with a high unmet clinical need.

As an example, fibroblasts can be acquired from a patient by skin biopsy, and T-cells from the blood. The RNA of these cells is then sequenced in order to compare the gene expression levels in the context of all other possible cell types.

Simultaneously, local transcriptomic regulatory networks are built around each regulatory gene (e.g. transcription factors) in the human genome to calculate and rank the effect of the genes on the desired cell conversion by querying large-scale regulatory networks. The optimal combination of key regulators is predicted to maximize network coverage while avoiding redundancies.

Once this optimal combination has been identified, the DNA sequence of each regulatory gene is encoded into delivery vectors (such as viral vectors), which are transduced into the fibroblast causing changes in DNA expression profile and therefore switching the genetic programs of the cell which induces the conversion of the fibroblasts into mature T-cells with cytotoxic capabilities.

This process can quickly and systemically be reproduced to enhance existing stem-cell forward reprogramming methods or to bypass development pathways altogether affecting a direct transdifferentiation between any starting cell type and any other clinically valuable cell type.

Published in Nature Genetics (2016)

Our

Science

Images adapted from Rackham OJL et al. A predictive computational framework for direct reprogramming between human cell types. Nature Genetics (2016)

Step 1 Calculation of contextual gene expression

Mogrify Direct Cellular Conversion Technology

Step 2 Identification and scoring of genes that require change from source to target cell

Mogrify Direct Cellular Conversion Technology

Step 3 Building local regulatory network of influence around each transcription factor (TF)

Mogrify Direct Cellular Conversion Technology

Step 4 Scoring of the conversion potential of each TF and optimization of network coverage with combinations of TFs

Applying Mogrify in Cell & Gene THERAPY

To ENHANCE

Efficacy

  • Enhances existing stem-cell forward reprogramming methods.
  • Bypasses development pathways altogether effecting 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.
  • 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)
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Collaborations
(Pancreatic, Lung,
Immune & Others)
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mogrify Mogrify Progress partner Expect to Partner