Science Matters

Understanding the most powerful new genetic technology

Boyce Rensberger

(7/2025) I want to tell you about one of the most revolutionary developments in science in decades. You may have read about this thing with the strange name of CRISPR. It’s a genetic technology that can seem like magic.

"It actually allows us to change human evolution if we want to," one of its discoverers has warned. That should get our attention. More immediately, dozens of clinical trials are underway for treatments that use CRISPR to diagnose or treat many different conditions from heart diseases to cancers to AIDS.

Scientists are already using CRISPR to make food crops more resistant to drought or disease. Some experts say CRISPR-modified crops will be in widespread use within 15 years. A whole new controversy about GMOs is certain.

So, this is a good time to try to get a sense of what it is. Stick with me through this piece, and I think you’ll come away with a fair grasp of the basics.

Recently you may have read, a baby was born with a rare and rapidly fatal disease caused by a mistake in its DNA. The mistake was very small, involving just a single letter out of the 3.2 billion letters that make up the human genome, a copy of which is carried in every cell. And yet scientists constructed a machine small enough to enter the baby’s bloodstream, find the mistaken letter, cut it out of the DNA strand and replace it with the correct letter. The molecule-sized CRISPR machine was custom made for this one baby’s genetic defect.

This molecular machine is a shape-shifter. It has moving parts—levers and latches that swing and swivel to grab other molecules and push them around. I’ll explain that as we go along with links to animations.

What’s new in the baby’s case is that CRISPR was used to repair a specific defect known only in this one baby, now ten months old and healthy. This bespoke version of CRISPR offers the promise of treatment for other extremely rare genetic diseases. But also treatments for more common diseases where a single mutation in one gene must be repaired.

Two years ago, the FDA approved a standardized CRISPR-based therapy for sickle cell anemia—a treatment that a few dozen people have received so far. That was done by re-activating a good gene that functions in the fetus but that is normally dormant in adults.

So, what is CRISPR, and why does it have a name pronounced like a drawer in the fridge?

Its history goes back to 1987 when scientists discovered a fascinating phenomenon in bacteria. Many of those one-celled organisms have a kind of immune system that protects them against viruses. Yes, bacteria get virus infections. As you may know, viruses are mainly packages of genes in the form of DNA or its molecular complement, RNA. The bacterial immune system consists of a molecule that recognizes certain sequences found in most virus genes and with the help of an enzyme that bacteria also carry, it cuts up the virus’s genes, stopping the infection.

These sequences (Are you ready for this?) are "clustered regularly interspaced short palindromic repeats." CRISPR is an acronym for that awkward term. (A palindrome is a sequence that reads the same in both directions. Viruses usually have these.)

In recent years, scientists realized that this system could be modified to recognize not virus sequences but any sequence in the genes of any cell. Molecular biologists have long known how to make DNA and RNA in any sequence they want. They just couldn’t splice it into a predetermined spot in a genome. A genome, you may recall, is the whole collection of genes (made of DNA) in a cell. Early forms of gene therapy used a shotgun method, randomly inserting new genes anywhere in the genome. Because CRISPR enables precise insertions, it opened vast frontiers in biological research and medical treatment. It is not only more accurate, but faster and cheaper.

The scientists who discovered this are Jennifer Doudna at the University of California-Berkeley and Emmanuelle Charpentier, director of the Max Planck Institute for Infection Biology in Berlin. Working together they did the basic science—and let me emphasize basic science—to understand these mechanisms and how to use them. And together they shared the 2020 Nobel Prize in chemistry.

CRISPR works something like a computer’s word processor with these four functions—find, cut, copy, and paste. The CRISPR "gene processor" has two main parts. The first is a short sequence of RNA that can search a cell’s genome and "find" a corresponding set of letters in the sequence that makes up DNA. Doudna calls it a "guide RNA." Scientists can synthesize any RNA sequence they like, typically making a segment that corresponds to the DNA sequence they want to find.

The second part of the CRISPR machine is a huge protein molecule originally found in bacteria. It’s called Cas, which is short for CRISPR-associated protein. Cas rides along with the guide RNA, unwinding the DNA double helix and separating the two strands so that the guide RNA can look for its corresponding sequence on one strand or the other.

The whole complex will bounce around randomly in a cell’s nucleus until it happens to find the right sequence. Then it will stick there while the second part of the Cas molecule changes shape again and cuts the DNA right where the guide RNA indicates, leaving two dangling ends.

When DNA breaks, which happens often naturally, cells use their own enzymes to splice the ends back together. At this point an optional third component of the CRISPR complex—the "copy" and "paste"—comes into play. It is a length of lab-made DNA bearing the correct sequence. This serves as a template that the cell, "thinking" that it is merely repairing a break, will automatically use to guide its repair. The result is the insertion of a new gene that may treat a disease or that may confer a new trait.

All this is slow to explain, but it happens in a fraction of a second in a living cell. And just as fast, if desired, in billions of cells simultaneously.

To see a short animation go to: bit.ly/CRISPRshort

To see a long animation go to: bit.ly/CRISPRanimation

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