New Compact Gene Therapy Tool Developed Through Rational Engineering
May 31 , 2025
Researchers at the McGovern Institute for Brain Research at MIT and the Broad Institute of MIT and Harvard have engineered a compact RNA-guided enzyme into a highly efficient tool for precise genome editing. Named NovaIscB, the new editor is derived from a bacterial enzyme and can be programmed to modify human DNA, regulate gene activity, or perform other targeted genetic alterations.
Due to its small size, NovaIscB offers a significant advantage for therapeutic use: it can be more easily delivered into cells, overcoming a major hurdle in gene therapy development. The protein’s versatility and compact design position it as a promising candidate for treating or preventing genetic diseases.
The research, published in Nature Biotechnology, was led by Feng Zhang, a pioneer in gene editing and the James and Patricia Poitras Professor of Neuroscience at MIT. Zhang also holds appointments at the McGovern Institute, the Broad Institute, and the Howard Hughes Medical Institute.
NovaIscB is based on IscB proteins—RNA-guided DNA-cutting enzymes that Zhang’s lab identified in 2021. These enzymes are part of the OMEGA system, considered evolutionary precursors to the widely known CRISPR-Cas9 system. Like Cas9, IscB enzymes use an RNA guide to locate and cut specific DNA sequences. By customizing the RNA guide, researchers can direct NovaIscB to virtually any target in the genome, enabling precise genetic interventions with potential therapeutic benefits.
SOURCE: https://news.mit.edu/2025/rationale-engineering-generates-compact-new-tool-gene-therapy-0528