A Powerful New Way to Edit DNA

In the late 1980s, scientists at Osaka University in Japan noticed unusual repeated DNA sequences next to a gene they were studying in a common bacterium. They mentioned them in the final paragraph of a paper: “The biological significance of these sequences is not known.”

Now their significance is known, and it has set off a scientific frenzy.

The sequences, it turns out, are part of a sophisticated immune system that bacteria use to fight viruses. And that system, whose very existence was unknown until about seven years ago, may provide scientists with unprecedented power to rewrite the code of life.

In the past year or so, researchers have discovered that the bacterial system can be harnessed to make precise changes to the DNA of humans, as well as other animals and plants.

This means a genome can be edited, much as a writer might change words or fix spelling errors. It allows “customizing the genome of any cell or any species at will,” said Charles Gersbach, an assistant professor of biomedical engineering at Duke University.

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Already the molecular system, known as Crispr, is being used to make genetically engineered laboratory animals more easily than could be done before, with changes in multiple genes. Scientists in China recently made monkeys with changes in two genes.

Scientists hope Crispr might also be used for genomic surgery, as it were, to correct errant genes that cause disease. Working in a laboratory — not, as yet, in actual humans — researchers at the Hubrecht Institutein the Netherlands showed they could fix a mutation that causes cystic fibrosis.

The technique is also raising ethical issues. The ease of creating genetically altered monkeys and rodents could lead to more animal experimentation. And the technique of altering genes in their embryos could conceivably work with human embryos as well, raising the specter of so-called designer babies.

“It does make it easier to genetically engineer the human germ line,” said Craig C. Mello, a Nobel laureate at the University of Massachusetts Medical School, referring to making genetic changes that could be passed to future generations.

Still, Crispr is moving toward commercial use. Five academic experts recently raised $43 million to start Editas Medicine, a company in Cambridge, Mass., that aims to treat inherited disease. 

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Breaking the Chain

A complex immune system found in bacteria is already proving useful in editing DNA and may lead to future therapies.

Snippet

RNA

Short, repeating

block of DNA

Enzyme

Cut

Edit

Cut

Repair

RNA

Spacer

Matching

sequence

of DNA

RNA made

from one

spacer

Disabled

gene

STORAGE  Researchers in the 1980s noticed that bacteria had small blocks of palindromic DNA repeated many times, with nonrepeated spacers of DNA stored in between. This pattern is a sophisticated immune system known by the acronym Crispr, for “clustered regularly interspaced short palindromic repeats.”

RECOGNITION  These spacers match pieces of DNA from viral invaders that bacteria or their ancestors have faced before. When needed, the DNA contained in the spacer is converted to RNA. An enzyme and a second piece of RNA latch on, forming a structure that will bind to strands of DNA that match the spacer’s sequence.

CUTTING  When a matching strand of DNA is found, the enzyme opens the double helix and cuts both sides. The double cut breaks the strand and disables the viral DNA. If a bacterium survives an attack by an unfamiliar virus, it will make and store a new spacer, which can be inherited by future generations.

EDITING  Researchers are learning how to use synthetic RNA sequences to control the cutting of any piece of DNA they choose. The cell will repair the cut, but an imperfect repair may disable the gene. Or a snippet of different DNA can be inserted to fill the gap, effectively editing the DNA sequence.

By The New York Times

Sources: Nature; Addgene

The pace of new discoveries and applications is dizzying. “All of this has basically happened in a year,” Dr. Weiss said. “It’s incredible.”

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