A CRISPR Way to Modify Damaged Genes
by Anisah Rafi
Only three years ago, Dr. Jennifer Doudna from the University of California at Berkeley developed a molecular scalpel that can be used to snip out defective genes. This innovation launched a genetic-engineering gold rush in 2012 as researchers raced to use Doudna’s new method: Clustered Regularly-Interspaced Short Palindromic Repeats (CRISPR). The tongue-twisting technology has little to do with keeping leafy greens fresh in the refrigerator. CRISPR is one of the latest biomedical engineering systems used to manipulate genomic DNA in almost any animal species and has the potential to produce new treatments and even cures for genetic diseases. Researchers can now use CRISPR to potently trim, disrupt, replace or add to an organism’s sequence of DNA, making targeted genetic modifications far faster and far less expensive than ever before.
Researchers in Doudna’s lab at UC Berkeley did not develop CRISPR through years of specifically tailored trial and error, but rather from trying to understand a fundamental concept of nature. Doudna’s research assessed how bacteria fight the flu. Bacteria have special enzymes that can cut open and modify invading viruses’ DNA at the site of the cut, which obliterates the virus. Recognizing that bacterial immune enzymes have a short template that attaches to specific strings of codons in viral DNA, Doudna wondered whether these enzymes could be modified to detect DNA sequences in any invading species.
The CRISPR method works to knock out genes, repress gene expression and up-regulate genes to increase their expression. CRISPR originated from a microbial immune system that contains DNA segments known as clustered regularly interspaced short palindromic repeats. Using a specialized editing enzyme, the biomedical engineering system pieces together DNA with a small portion of RNA that guides the instrument to where researchers want to introduce cuts or other genomic changes. Consequently, Dr. Doudna’s research used bacterial immune systems that employ viral RNA molecules to specifically target and destroy foreign DNA. CRISPR can be used as a molecular tool for precise genomic engineering to recognize and modify viral sequences in various kinds of cells — “You can take it out, you can change it, or you can add to it,” says Doudna.
While The Human Genome Project gave the world a chance for extensive exploration of the human genome, Doudna’s new model provides a means for intervention. “You’ve got the book,” says Doudna, “And you can see there’s a word that’s incorrect on page 147. But how do I get in there and erase that word and fix it?” This technique gives researchers the flexibility to artfully alter the expression of genes. Efficacy comparisons show that the CRISPR model can generate genomic mutations through particular interventions about 100 times more efficiently than other gene-modifying techniques, such as Transcriptor Activator-Like Effector Nuclease (TALEN). Studies reveal that CRISPR’s advantage over other genomic-engineering systems is its ability to target only mutation-containing genes, without affecting the healthy gene in a pair.
Craig Mello, Ph.D., of the University of Massachusetts Medical School, and 2006 Nobel Prize winner in Physiology or Medicine, has developed a biotech company called CRISPR Therapeutics. The institute constructs treatment therapies for patients with certain genetic blood diseases, such as sickle cell and thalassemia. Dr. Mello uses the CRISPR approach to remove blood cells from patients’ bone marrow, repair damaged genes and subsequently re-implant the repaired cells to the patients. Consequently, CRISPR is a proven cost-effective method of controlling genetic diseases using a patient’s own cells.
Future medical implications with CRISPR are astounding. For instance, partners who each carry the recessive allele for cystic fibrosis could have the option of using in-vitro fertilization to create an embryo and employing CRISPR to fix the damaged gene. As the biotechnological capabilities of genomic engineering rapidly advance, many researchers believe that CRISPR will be the next great leap forward in genetic therapeutics and personalized medicine.