CRISPR’s next act: the companies editing the epigenome to treat disease

Key Points:

• Amber Salzman, initially uninterested, became CEO of Epicrispr Biotechnologies after learning the company aimed to develop targeted epigenetic therapies for facioscapulohumeral muscular dystrophy (FSHD), a disease affecting her family.
• Epicrispr and other companies are pioneering targeted epigenetic editing, which modifies chemical markers on DNA to switch genes on or off without altering the DNA sequence itself, offering a potentially safer alternative to traditional gene editing.
• The technology uses a modified CRISPR system with a "dead" Cas enzyme that binds DNA without cutting it, allowing precise control of gene expression and reducing risks of off-target mutations and DNA damage.
• Advances include the use of smaller Cas proteins like Cas12F for easier delivery into cells via harmless viruses, and improvements in components like methyltransferases to enhance efficiency and specificity.
• Clinical trials are underway for epigenetic therapies targeting diseases such as hepatitis B and high cholesterol, with promising preclinical results showing significant reduction in disease markers after a single treatment.