Revolutionizing disease treatment, researchers unveil NovaIscB, a compact RNA-guided enzyme engineered to precision-edit human DNA.
Compact Gene Editing Tool Offers New Hope for Disease Treatment
Researchers at the McGovern Institute for Brain Research at MIT have engineered a compact RNA-guided enzyme from bacteria, making it an efficient editor of human DNA. The protein, called NovaIscB, can be adapted to make precise changes to the genetic code, modulate the activity of specific genes, or carry out other editing tasks.
Advantages of NovaIscB
The compact size of NovaIscB simplifies delivery to cells, making it a promising candidate for developing gene therapies to treat or prevent disease. Unlike tools developed using Cas9, which can be bulkier and require more complicated delivery strategies, NovaIscB-based tools are easy to package inside a single adeno-associated virus (AAV). This makes them ideal for safely delivering gene therapy to patients.
Gene therapies involve the use of genes to prevent or treat diseases.
They work by introducing healthy copies of a faulty gene into cells, allowing them to produce functional proteins.
Gene therapies have shown promise in treating inherited disorders such as sickle cell anemia and cystic fibrosis.
According to the National Institutes of Health (NIH), over 2,000 clinical trials are currently underway for gene therapy treatments.
The first FDA-approved gene therapy treatment was approved in 2017 for a type of leukemia.
Engineering NovaIscB
The team led by Feng Zhang leveraged information about the diversity of bacterial IscBs and their evolution to optimize NovaIscB. They discovered that certain segments, such as REC, were essential for interaction with human DNA. By making strategic changes to the protein’s structure, using artificial intelligence tools like AlphaFold2, they generated a protein that was over 100 times more active in human cells than the original IscB.
Feng Zhang is a Chinese-American molecular biologist who pioneered the development of optogenetics and made significant contributions to the field of gene editing.
He was awarded the 2018 Breakthrough Prize in Life Sciences for his work on CRISPR-Cas9 technology.
Zhang's research focuses on understanding neural circuits and developing new tools for neuroscience.
He is a professor at MIT and has published numerous papers on his groundbreaking discoveries.
Applications of NovaIscB
NovaIscB demonstrates its potential as a scaffold for various genome editing tools. It biochemically functions similarly to Cas9, making it easy to port over optimized tools. Researchers have used NovaIscB to replace specific letters of the DNA code in human cells and change the activity of targeted genes.
Genome editing refers to the direct manipulation of an organism's genome, allowing scientists to modify its DNA sequence.
This technology uses enzymes called nucleases to make precise cuts in the DNA, enabling researchers to insert, delete, or replace specific genes.
Genome editing has numerous applications in medicine, agriculture, and biotechnology, including treating genetic diseases, developing novel crops, and producing biofuels.
Therapeutic Potential
The team created a tool called OMEGAoff that adds chemical markers to DNA to dial down the activity of specific genes. They demonstrated its potential by programming OMEGAoff to repress a gene involved in cholesterol regulation, leading to lasting reductions in cholesterol levels in mice.
Future Directions
The researchers hope that NovaIscB can be used to target genome editing tools to most human genes and that other labs will adopt their evolution-guided approach to rational protein engineering. By learning from the natural diversity of biological systems, they aim to make gene editing tools more efficient and effective.
