The human genome, which encompasses all of our genetic material, is an exhaustive set of instructions complete with mechanisms to replicate and correct itself. The majority of the time, these mechanisms work faultlessly, correcting mutations in our DNA almost immediately after they occur. But once in a while, these mechanisms falter and the mutations become permanent fixtures in our DNA, causing genetic conditions like Parkinson’s disease, sickle cell anemia, and cystic fibrosis. While scientists have long since attempted to correct these mutations with various gene editing mechanisms, they were often hindered by a lack of accuracy and control. But in recent years, with the emergence of technologies like CRISPR, treating previously “incurable” genetic diseases has become increasingly viable.
CRISPR, which stands for “clusters of regularly interspaced short palindromic repeats,” uses crRNA (CRISPR RNA) and tracrRNA (trans-activating crRNA) as a guide and the Cas9 enzyme as scissors to cut the DNA at specific, predetermined sites . Once the DNA has been cut, scientists can introduce a DNA template, which the cell uses as a pattern to fill in the gap, correcting the mutation by replacing it with the desired sequence. This sequence is then fully incorporated into the DNA by its own repair mechanisms. The unmatched accuracy of the CRISPR system is in part due to the fact that the Cas9 enzyme only targets DNA sequences adjacent to PAMs, or "protospacer adjacent motifs," so cutting is less random .
While CRISPR is relatively accurate, it still has a way to go before it is ready to be used as a clinical treatment of genetic disease. With the development of this technology comes a slew of ethical questions. While CRISPR can be used to correct mutations in specialized embryonic stem cells that are cultured to produce the necessary replacement tissues, it can also be used to directly and permanently edit reproductive or embryonic cells of the germline . Many scientists are apprehensive that we do not yet fully know all of the possible repercussions of germline editing, in which the changes are be passed on to future descendants. But researchers at the Broad Institute of MIT and Harvard have recently found a solution to this problem by developing a new CRISPR technology called REPAIR.
REPAIR, which stands for “RNA Editing for Programmable A to I Replacement,” targets and edits RNA, a nucleic acid that uses instructions from DNA to synthesize proteins. REPAIR uses the Cas13 enzyme to target RNA transcripts to change bases from adenosine to inosine (read as guanosine), reversing the guanosine-to-adenosine mutations and restoring gene function . This technology, which corrects the RNA without physically cutting it, allows scientists to control gene expression, and not necessarily shut it down completely as with other technologies. Scientists are already testing its therapeutic potential by using it to alter human cells with mutations that cause anemia and other diseases . The hallmark of REPAIR is that it can cause genetic alterations without permanently altering the germline, allowing scientists the flexibility to use it during acute disease treatment, organ transplants, and much more.
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Edited 2/1/18 11:53PM to include missing first paragraph.