A major focus in the field of biotechnology is the development of tools for editing the genomes of living cells. Such techniques have a range of applications, from creating engineered bacteria to curing some of the world’s most serious diseases. One of the most exciting advancements to come out of the field of genetics is the CRISPR-Cas9 gene-modification technique, which is powerful yet simple enough for amateur scientists to use. CRISPR stands for “clustered regularly interspaced short palindromic repeats,” because each CRISPR unit consists of repeated DNA base-pair sequences that read the same forward or in reverse. A “spacer” separates the sequences, which act almost like palindromic pieces of Morse code.
CRISPR technology has the potential to allow biologists to edit virtually any genetic code, including the human genome. Over the three years that have passed since the technology became available, researchers have applied it to investigations of everything from sickle-cell anemia to cystic fibrosis. Some researchers have even used it to treat HIV by removing cellular receptors that the virus exploits when infecting the human immune system. However, CRISPR’s biggest impact is likely to be on diseases caused by genetics, whether they are caused by a single mutation, such as Huntington’s or sickle cell, or hundreds of malformations, like Alzheimer’s and diabetes.
A Closer Look at How CRISPR Technology Works
CRISPR units cut through DNA and replace nucleotide bases with new sequences, but they do not have the accuracy needed for scientific consistency. To achieve desired reliability, researchers use an RNA-based guide called a Cas (CRISPR associated) gene. The Cas gene looks for a specific sequence of nucleotides, usually a 20-pair sequence, and then binds to that site. Considering that the human genome consists of 20,000 genes, the ability to choose sites with a 20-nucleotide sequence can provide the precision necessary to make the technology a viable option. Together, the CRISPR/Cas system can silence the expression of a single gene virtually anywhere on a strand of DNA.
The biological mechanism behind CRISPR relates to acquired immunity in single-celled organisms. For a long time, researchers assumed that single-celled organisms only had innate immunity as part of the genetic sequence and that acquired immunity, which responds to and learns from contact with the environment, was reserved for multicellular organisms.
In truth, bacteria use a complicated system to obtain immunity against specific viruses so that they can respond more rapidly to a future infection. This system operates by creating a “memory” in much the same way as T-cells do in the human immune system to keep people from repeatedly getting sick from the same disease. T-cell immunity is what makes vaccination so powerful.
To modify genetic code, CRISPR technology uses a very similar mechanism. Bacteria produce strands of RNA that bind to the RNA of the invading virus. When they combine, new strand complexes with Cas9, a nuclease that has the ability to cut DNA. When the guide RNA finds its target in the viral genome, Cas9 cuts the DNA to disable the virus. As researchers studied the system, they realized they could change the guard RNA to edit virtually any DNA strand.
Potential Applications of CRISPR Technology
The benefits of CRISPR genome editing extend beyond humans and animals. Two years ago, geneticists from China edited the wheat genome to give it immunity against powdery mildew, which remains one of the most widespread plant pathogens on the planet. The edit involved removing only three genes from the wheat DNA. Other researchers have used CRISPR technology to protect tomatoes and cotton against the yellow leaf curl virus. Last year, Japanese scientists edited the genes that control tomato ripening to increase their shelf life exponentially. With CRISPR, scientists may be able to create more robust crops that provide higher yields and greater tolerance against pests and drought. Notably, the same can beaccomplished with multiple generations of genetic work or the introduction of foreign DNA into a plant’s genome, which is the conventional GMO process.
Certainly, CRISPR technology also presents certain dangers. Researchers now know enough about genome editing to make it potentially hazardous, especially when long-term implications remain unknown. The technology also brings up a number of ethical issues. For example, the first modified human embryo recently caused a great deal of controversy. Genetic editing gives doctors the chance to cure diseases and defects prior to birth, but the results of something going awry could prove devastating. However, these types of treatments would remain very rare because people born with a genetic disease could undergo somatic cell editing for treatment.