Genetic 'typo' corrector

Meeri N. Kim, For The Inquirer Last updated: Sunday, May 18, 2014, 8:51 AM Posted: Saturday, May 17, 2014, 3:55 PM

Imagine a document 25,000 words long - about 100 pages, double-spaced - with one small error. Within the text of our genetic code, a single change like this can lead to a life-threatening disease such as sickle-cell anemia or cystic fibrosis.

Most of these single-gene disorders have no cure. But using a new technique, doctors may one day be able to correct the genetic typo by replacing a harmful mutation in the genome with healthy DNA.

Introducing CRISPR (clustered regularly interspaced short palindromic repeats), a genetic editing tool that can cut and paste parts of any living animal's DNA. Although in its infancy, the system is generating excitement among scientists for its ease of use, accessibility, and vast potential.

The CRISPR system enables researchers to make a small chain of custom-made molecules, called a guide RNA, and a Cas9 enzyme. The guide RNA is like the search function of a word processor, running along the length of the genome until it finds a match; then, the scissorslike Cas9 cuts the DNA. CRISPR can be used to delete, insert, or replace genes.

"We didn't used to think that we had the tools to correct mutation in humans," said Penn Medicine cardiologist Jonathan Epstein, who just began using the technique in his lab. "The advantage of CRISPR is that we can."

For instance, sickle-cell anemia is caused by a mutation in chromosome 11 that causes red blood cells to be crescent-shaped, sticky, and stiff. They end up stuck in the blood vessels, keeping enough oxygen from reaching the body. While the disease can be treated with bone marrow or stem cell transplants, most patients cannot find well-matched donors.

Here's where CRISPR can help. Biomedical engineer Gang Bao of the Georgia Institute of Technology aims to use the system to repair the DNA of a patient's own stem cells, so no outside donor would be needed. The stem cells would be extracted from the patient's bone marrow, their mutations replaced with normal DNA, and inserted back in. The hope is that the gene-corrected stem cells would then begin making normal red blood cells.

The treatment works in mice, and Bao foresees human trials within a few years.

Continued here:
Genetic 'typo' corrector