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A new technology to simultaneously badyze the functions of hundreds of genes with a resolution reaching the single cell level was developed by scientists at Mount Sinai Hospital. The method is based on a bar coding approach using a new protein.
The sequencing of the first human genome in the early 2000s revealed a set of more than 20,000 genes encoding a protein, scientists have not yet been able to characterize the many functions. of the individual gene. Without this information, our understanding of how the human genome works – and how to use it to predict, prevent, treat and even cure a disease – is limited.
In 2012 and 2013, scientists put together a powerful new approach to gene editing. called CRISPR, which can be used to determine gene functions. CRISPR has taken the scientific world by storm, but researchers are still struggling to use CRISPR to study the thousands of genes and their multiple possible roles.
Pro-codes
The new technology developed by scientists from the Icahn School. of Medicine at Mount Sinai Helps Meet the Genomics Challenge of Analyzing the Genome on an Unprecedented Scale The research, led by Dr. Aleksandra Wroblewska, Postdoctoral Fellow and Maxime Dhainaut, Ph.D., is a new tool for bar code coding and tracking CRISPR using synthetic proteins called epitopes.
Protein bar codes, called Pro codes, allow hundreds of CRISPRs to be used together to neutralize a multitude of genes.
Although there are CRISPR clustering technologies, these approaches rely heavily on DNA as a barcode and allow only low-resolution badysis of gene function. Through the Pro-Code technique, Mount Sinai researchers have been able to demonstrate a way for scientists to further characterize the biological effects of a gene.
Purpose of Cancer Immunotherapy
In their study, researchers used Pro-Code technology. search for genes needed by the immune system to protect against cancer. They generated CRISPRs to target the suppression of genes suspected of immune regulation and coupled them with Pro-Codes.
Pro-Code / CRISPR libraries were then introduced into bad cancer cells and tumors were tested with killer T cells designed to recognize cancer cells. Most cancer cells were rapidly cleared by T cells. However, some cells survived death.
Pro-Code technology was used to determine which genes were lost in resistant cells, some with an unrecognized role in the sensitization of cancer cells in the human body. immune system. Studies have also identified a negative regulator of immune control point PD-L1, a major clinical target for cancer immunotherapy.
"There is still a lot of work to be done to fully understand the human genome. We still do not know what most genes do and how they are connected. "" Pro-Code technology could dramatically accelerate one of the major goals of the post-genomic era: the annotation of the human genome. This discovery will be the key to discover genes responsible for diseases that may lead to new therapeutic targets. This has already brought us new insights into cancer immunology. "
explains lead author Brian Brown, Ph.D., badociate professor of genetics and genomics sciences and badociate director of the Institute of Immunology of the Icahn Institute .
Aleksandra Wroblewska, Maxime Dhainaut, Benjamin Ben-Zvi, Samuel A. Rose, Eun Sook Park, El-Ad David Amir, Anela Bektesevic, Alessia Baccarini, Miriam Merad, Adeeb H. Rahman, Brian D. Brown
Protein barcodes allow the development of high-dimensional single cell CRISPR Screens
Cell (2018). DOI: 10.1016 / j.cell.2018.09.022
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