Skip to content
Technology — Science — Medicine — News — Medical-conditions — Engineering — Health — Graduate — Labs

Method for Activating Genes Discovered

Modified gene-editing tool by MIT researcher Feng Zhang promises simplified analysis of individual genes and identification of disease-linked genes.

,   and  Administrator
3 min read
Enhanced CRISPR/Cas9 application from MIT's Feng Zhang aims to simplify gene function...
Enhanced CRISPR/Cas9 application from MIT's Feng Zhang aims to simplify gene function identification and disease-related gene discovery for researchers.

Method for Activating Genes Discovered

MIT researchers have made a groundbreaking advance in the CRISPR/Cas9 gene-editing system by creating a method to reliably activate any gene in living cells.

This innovation, led by Feng Zhang, the W.M. Keck Career Development Professor in Biomedical Engineering at MIT, could significantly aid scientists in understanding the functions of individual genes. According to Zhang, this approach enables rapid functional screens of the entire genome, allowing scientists to identify genes associated with specific diseases.

In a study published in Nature, Zhang and his colleagues identified several genes that contribute to melanoma cells becoming resistant to a cancer drug. Silvana Konermann, a graduate student in Zhang's lab, and Mark Brigham, a McGovern Institute postdoc, are the paper's lead authors.

Traditionally, the CRISPR system has relied on cellular machinery used by bacteria to defend against viral infection. Previous attempts to use CRISPR to activate genes have been limited by the difficulties of working with proteins engineered to target DNA at specific sites. Moreover, attempts to use CRISPR to activate genes by inactivating the DNA-cutting enzyme in the Cas9 complex and linking it to activation domains have been inconsistent.

In the new study, Zhang and his colleagues, including Osamu Nureki and Hiroshi Nishimasu at the University of Tokyo, overhauled the CRISPR-Cas9 system based on an analysis of the structure formed when Cas9 binds to the guide RNA and its target DNA. They discovered that small loops of the RNA guide, which poke out from the Cas9 complex, could be better points of attachment for activation domains, allowing them more flexibility in recruiting transcription machinery.

Using this revamped system, the researchers activated about a dozen genes that had proven difficult or impossible to turn on using previous methods. Each gene showed at least a twofold boost in transcription, and for many genes, the boost was multiple orders of magnitude.

Having demonstrated the system's effectiveness, Zhang's lab created a library of 70,290 guide RNAs targeting all of the more than 20,000 genes in the human genome. By screening this library, they identified genes that confer resistance to a melanoma drug called PLX-4720. These genes could help cancer cells survive the treatment, allowing the cancer to recur.

The new technique could aid researchers in discovering new cancer drugs that prevent tumors from becoming resistant. Scientists have tried to perform large-scale screens like this by delivering single genes via viruses, but this method does not work with all genes. This new technique could allow for the sampling of a broader spectrum of genes that might be playing a role.

In addition to cancer research, the lab plans to use this technique to screen for genes that, when activated, could correct the effects of autism or neurodegenerative diseases such as Alzheimer's. Zhang also intends to make the necessary reagents available to academic labs through the Addgene repository.

The research was funded by several organizations, including the National Institute of Mental Health, the National Institute of Neurological Disorders and Stroke, and Bob Metcalfe. This advance in the CRISPR/Cas9 system represents a significant step forward in gene regulation, expanding CRISPR's capacity beyond cutting DNA to reliably switching genes on in living cells.

  1. The advancement in the CRISPR/Cas9 gene-editing system, led by Feng Zhang, is expected to aid scientists in comprehending the functions of individual genes in health and medicine.
  2. The new method in gene activation could potentially identify genes associated with specific medical-conditions, such as cancer or neurological diseases.
  3. The innovation in gene engineering could significantly contribute to technology development, potentially leading to the discovery of new drugs for various ailments.
  4. In a recent study published in Nature, Zhang and his team discovered several genes contributing to melanoma cells' resistance to a cancer drug.
  5. The revamped CRISPR-Cas9 system developed by Zhang and his colleagues outperformed previous methods in activating genes that were difficult or impossible to switch on.
  6. The lab plans to use this new technique to screen for genes that, when activated, could potentially correct the effects of mental conditions like autism or neurodegenerative diseases such as Alzheimer's.
  7. The research was financially supported by organizations like the National Institute of Mental Health, the National Institute of Neurological Disorders and Stroke, and Bob Metcalfe, signifying the significance of this advance in the field of science and technology.

Read also:

    Related

    Latest