PNAfuse™ Epigenetic Reprogramming Technology
Our precision epigenetic rewriting platform. It uses modular peptide nucleic acid anchors to home in on precise coordinates within a target gene, recruiting natural modifiers to rewrite the epigenome without ever cutting DNA.
PNAfuse™ Feasability Data
Targeted SOX2 Up-regulation
In this feasibility study, the >20-fold transient activation of SOX2, a Yamanaka OSK factor (OCT4, SOX2, and KLF4) that are thought to initiate a cascade of cellular rejuvenation events that remodel chromatin structure and restore a youthful epigenetic landscape, ultimately restoring PGC-1α (PPARGC1A) expression and activity... a master regulator of mitochondrial function and oxidative metabolism.
Modular Scaffold Designs
Gene Activation
VP64 is a synthetic activation domain that recruits the cell’s transcriptional machinery to dramatically increase expression of target genes. By amplifying endogenous gene activity without altering DNA sequence, VP64 enables robust and programmable gene activation from a single PNAfuse binding event.
Gene Insertion
A recruited transposase enables site-specific insertion of therapeutic DNA payloads into predefined genomic locations. This transforms PNAfuse from a transient regulator into a platform capable of durable genetic modification without viral vectors.
Recruit Endogenous Transcription Factors
Endogenous (Sp1, p65) aptamers function as a programmable docking factor that can recruit engineered transcriptional complexes to selected genomic loci. This provides a modular framework for building custom gene-regulatory circuits directly on endogenous chromatin.
Fluorescent or Bioluminescent Reporters
Horseradish peroxidase (HRP), Nanoluc, and GFP serve as a sensitive reporter that converts molecular recruitment into a measurable signal. This allows rapid quantification of target engagement, optimization of construct design, and direct monitoring of therapeutic activity.
Histone Acetylation
p300 is a histone acetyltransferase that opens chromatin by depositing activating histone acetylation marks. Recruitment of p300 can convert inaccessible genomic regions into transcriptionally active states, producing durable increases in target gene expression.
Gene Methylation/De-methylation
Tet1 actively removes repressive DNA methylation marks through targeted DNA demethylation. This enables reactivation of silenced genes and offers a powerful mechanism for epigenetic reprogramming, cellular rejuvenation, and restoration of youthful transcriptional states.
EPH-101 Mechanism of Action
EPH-101
By targeting the epigenetic drivers of muscle aging rather than simply treating symptoms, EPH-101 aims to provide a disease-modifying approach for age-related frailty and functional decline. We believe that mitochondrial restoration, muscle regeneration, youthful gene expression, improved tissue function
PNAfuse™ Formulation
