METHODS FOR TREATING MENDELIAN DISORDERS OF THE EPIGENETIC
MACHINERY
JHU REF: C13083
Invention novelty: A genetically encoded histone reporter allele system which can be utilized for high throughput screening in in vitro cellular systems.
Value Proposition: Epigenetic modifications are thought to be one of the critical mechanisms that mediate gene-environment interactions. However, despite a number of well-known drugs affecting epigenetics, few epigenetic therapies have made it to clinical practice. Johns Hopkins researchers have developed genetically encoded histone reporter allele system which can theoretically be used to monitor activity of any histone maintenance machinery component in live cells. This system offers the following advantages:
- A genetically encoded indicator system that allows fluorescent quantification of ANY histone maintenance enzyme for which there is a known reader and histone tail.
- The indicator system has the potential for single cell resolution and is applicable for in vitro high throughput screening in cellular systems.
- The indicator system has the potential to be introduced into laboratory animals since it is genetically encoded, and can thereby either be used to study the activity of the corresponding histone maintenance system postmortem in any organ, or alternatively as a possible biomarker using lymphocytes from live animals or to create a cellular assay from any cell type that can be cultured from mice.
- The indicator system is not FRET (Förster resonance energy transfer) based and can be utilized by any fluorescent platform that measures fluorometry and/or used for fluorescent activated cell sorting (FACS).
Technical Details:
Johns Hopkins researchers have created a acetyl reporter protein that quantifies the activity of the acetylation machinery and comprises an H4 tail on one end (the target for acetylation) and a TBP associated factor II (TAFII) bromodomain on the other end of the reporter protein. They also created an H3K4 trimethylation reporter based on the H3 tail on one end and the TBP associated factor ILL (TAFIII) homeodomain on the other end; the TAFIII homeodomain only identifies and binds to trimethylated K4 on H3. They are also creating a corresponding transgenic mouse model for each reporter allele, one to monitor global acetylation activity and one to monitor global H3K4 trimethylation activity.
Looking for Partners:To developed and commercialize for assay development and epigenetic therapeutic development
Stage of Development: Discovery, Preclinical
Data Availability: Under CDA/NDA
Patent Status: Pending
Publication(s)/Associated Cases: None at this time
Categories: Discovery/Research tools
Keywords: Epigenetics, Histone, alleles, H3K4
