David Rufino-Ramos PhD

PI / Investigator: David Rufino-Ramos PhD - Harvard Medical School

Award Type: Postdoctoral Fellowship

Grant Title: Developing and delivering of novel gene editing technologies to contract GAA repeats in Friedreich's ataxia

Lay Summary:

One promising therapeutic approach for FA is to eliminate the root cause of the disease by contracting the expanded GAA repeat in the FXN gene using genome editing technologies. Genome editing technologies have revolutionized research by democratizing genetic changes and expanding our ability to make customizable modifications to the human genome.

In this project, Dr Rufino-Ramos will explore a variety of CRISPR-based editing tools to contract the GAA repeats, which will correct the FXN defect and thereby restore frataxin expression. To minimize unwanted genetic modifications in other parts of the genome (called off-targets) by restricting the duration of expression of the genome editing tools, Dr Rufino-Ramos proposes to deliver these enzymes in a transient manner using cell derived vesicles, called extracellular vesicles (EVs).

EVs encapsulate, protect, and permit targeting the CRISPR tools to the intended cells for a short period of time—long enough to contract the GAA repeats but short enough to minimize the risk of unwanted genome edits. Together, this research will explore safe and effective methods to treat FA through synergistic optimization of genome editing and delivery approaches.

Co-Sponsor: fara US