Clustered regularly interspaced short palindromic repeats, also known as CRISPR, evokes a sense of unease in many people, especially since the term has become synonymous to gene editing technology.
Scientists, however, continue finding ways to use the technology to solve many medical concerns all over the world, and that is exactly what a team of researchers from Broad Institute did when they developed the Specific High-sensitivity Enzymatic Reporter unLOCKing (SHERLOCK).
The acronym may sound a little forced but the actual tool will be very helpful in case of health-related outbreaks, especially since it can be designed for paper-based tests.
CRISPR's Role
As mentioned earlier, CRISPR has already become synonymous to gene editing using the DNA-targeting Cas9 enzyme but this is not the case with SHERLOCK. First co-authors Omar Abudayyeh and Jonathan Gootenberg, graduate students from MIT and Harvard, respectively, focused on using the RNA-targeting Cas13a enzyme to develop a sensitive diagnostic tool that can detect small amounts of biological materials. SHERLOCK also releases diagnosis faster than conventional methods.
"One thing that's especially powerful about SHERLOCK is its ability to start testing without a lot of complicated and time-consuming upstream experimental work [...] This is just the beginning," study co-author Pardis Sabeti says.
What Is SHERLOCK?
SHERLOCK is an extremely sensitive CRISPR-based diagnostic tool that scientists and medical practitioners can use to detect even the faintest presence of virus and bacteria from a patient's blood or urine sample. To illustrate its potency, SHERLOCK can detect even a single molecule of DNA or RNA of the target particle, virus, or bacteria — up to 10-18 — in an infected sample.
How Does SHERLOCK Work?
Abudayyeh and Gootenberg took advantage of the "collateral cleavage" in RNA that was described by Professor Feng Zhang's team in a previous CRISPR study. According to the previous study, the Cas13a enzyme can be programmed to target specific sequences in viral and bacterial cells and still remain active afterwards. In order to test this discovery, the study co-authors spiked Zika- or dengue-infested samples with fluorescent reporter RNAs. The reporter RNAs would then cut any molecule containing the target virus and then cut other fluorescent reporters, creating a signal that would allow the scientists to determine if a sample is infected.
SHERLOCK is, of course, smarter and more capable than just sending detectable signals. In fact, SHERLOCK can already be applied to diagnose several diseases.
SHERLOCK Applications
The proponents demonstrated a wide variety of uses for the diagnostic tool they created and, according to them, SHERLOCK can do the following things and more:
• Detect Zika virus in blood and urine samples within hours and distinguish between its African and American strains
• Distinguish between Zika and dengue
• Discriminate different types of bacteria, like E. coli
• Detect cancer cell mutations
• Detect antibiotic resistance genes
• Read human genetic information from saliva sample
"[If] SHERLOCK can be developed to its full potential it could fundamentally change the diagnosis of common and emerging infectious diseases," study co-author Deb Hung says. Hung is also the co-director of Broad Institute's Infectious Disease and Microbiome Program.
Watch the video below to know more about SHERLOCK.
