What is CRISPR and How Can It Help Cancer Research?

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CRISPR, a powerful new tool for editing the DNA instruction manual in animals and humans, is proving a boon to cancer research. Scientists say CRISPR has dramatically accelerated the process of making animal models of cancer and is speeding the search for new molecular targets for cancer drugs. The technique is also being used in efforts to improve immunotherapies and other cancer treatments.

CRISPR can edit the DNA instruction in human and animals. A chromosome (pictured) is made up of protein and a single DNA molecule.

CRISPR can edit the DNA instruction in human and animals. A chromosome (pictured) is made up of protein and a single DNA molecule.

More accurately known as the CRISPR-Cas9 system, it was first applied in 2013 to human genome editing – the process of modifying the DNA blueprint in humans as a way of altering traits.

CRISPR-Cas9 evolved in nature as a molecular mechanism that bacteria use to defend against viral invaders. It consists of two parts: A guide molecule that can identify a precise location in the genome – the complete set of genes in an animal or human — and enzymes that can cut the DNA at that point, allowing existing genes to be removed and new ones added.

What Does CRISPR Mean for Cancer Research?

Cancer is a disease caused by mutations and other changes in genes that control cell growth and division, leading to the formation of tumors. CRISPR-Cas9 makes it possible to alter the function of many genes at once – turning them on or off, for example, and in a simpler, faster, and less expensive fashion than with previous methods. That will make it easier for scientists to create animal models of different types of cancer, and better study cancer development.

CRISPR-Cas9 has been used to uncover vulnerabilities in rare children’s cancers, according to William Hahn, MD, PhD, chief of the Division of Molecular and Cellular Oncology at Dana-Farber. He and his colleagues used the technique to silence several hundred different genes in a sample of a pediatric sarcoma, then observed how the loss of the genes’ function affected the tumor cells. When used with two other methods, this strategy identified two proteins that the sarcoma depended on, and which might be targets for precision therapies.

In another application of the method, researchers at Dana-Farber/Boston Children’s Cancer and Blood Disorders center used CRISPR-Cas9 genome editing to test the functions of thousands of tumor genes in mouse models, revealing new drug targets that could potentially enhance the effectiveness of PD-1 checkpoint inhibitors, a form of cancer immunotherapy.

Alison Taylor, PhD, a postdoctoral fellow in the laboratory of Matthew Meyerson, MD, PhD, has inserted CRISPR into cells in the laboratory to delete a large segment of a human chromosome to create a model of a type of lung cancer.

Previously, to make a mouse model of a disease or cancer type, genetic changes had to be made in the embryo of a laboratory animal such as a mouse, so that the altered genes were present in the adult animal when it grew to maturity. With CRISPR-Cas9, modifications can be made directly in the somatic cells of adult mice.

Scientists have reported making animal models of lung, liver, pancreatic, brain, and blood cancers using CRISPR-Cas9 tools.

Meanwhile, it may not be long before scientists make the first attempts to improve cancer treatment in humans using CRISPR techniques. Several clinical trials reportedly will be undertaken in China, and at least one has been planned in the United States. In the latter instance, the technique would be used to change immune cells to make them better at killing cancers.

Learn more from Dana-Farber about the latest in cancer research.

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