Sherlock Biosciences, the young company that is quickly making deep inroads in the CRISPR molecular diagnostics world, is not going to do it alone. Sherlock announced today that they are joining forces with two partners — the Bill & Melinda Gates Foundation and the lateral flow company Mologic — to turn their goals into a reality as quickly as possible. The partnership, they hope, will lead to the to development of a simple, cost effective, rapid and highly sensitive test for infectious diseases.
Sherlock launched just eight months ago to create a new generation of molecular diagnostics using CRISPR and synthetic biology. The range of applications for this technology is vast, including oncology, infectious disease, low-resource settings, agriculture, and at-home testing. This collaboration will combine Sherlock’s expertise in nucleic acid sensing with Mologic’s lateral flow to develop simple molecular diagnostics for use at various settings, including low resource and home settings.
Sherlock has two core technologies. One, termed “Sherlock” is an evolution of CRISPR technology that can detect unique DNA or RNA sequences in any organism or pathogen. The method, is a method for single molecule detection of nucleic acid targets and stands for Specific High Sensitivity Enzymatic Reporter unLOCKing. It works by amplifying genetic sequences and programming a CRISPR molecule to detect the presence of a specific genetic signature in a sample, which can also be quantified.
As described in the video above, Cas13 cleaves RNAs that are recognized by the guide RNA, but it can also cleave other RNA molecules at the same time. This is known as collateral activity. When this CRISPR system is attached to a reporter molecule, the enzyme cleavage breaks apart a reporter molecule and releases a signal in the form of color. This signal can be adapted to work on a simple paper strip test, in laboratory equipment, or to provide an electrochemical readout that can be read with a mobile phone.
“We want to develop a test that can be done as easily as a pregnancy test” notes Rahul Dhanda, CEO of Sherlock. The opportunity that this partnership brings, he explains, is to develop something that is “rapid, sensitive and simple”.
Mologic, headquartered in the United Kingdom, has specialized in lateral flow and rapid diagnostic technologies since 2003. Mologic’s founder, Paul Davis, PhD, was the originator of the Clearblue pregnancy test that was launched in 1988 as the world’s first commercial application of lateral flow technology.
Mologic developed their Centre for Advanced Rapid Diagnostics (CARD) program in 2016 with support from the Bill & Melinda Gates Foundation to redefine and re-engineer the critical components of the lateral flow immunoassay. Just two years later, CARD developed a rapid, ultra-sensitive, visually read and electricity free detection platform first demonstrated with malaria and HIV.
When Sherlock initiated conversations with the Gates foundation with similar ideas, the three organizations came together to decide how they could achieve their shared goals. Instead of Sherlock spending years building up their engineering capabilities, Dhanda asserts, they have gained decades worth of experience by partnering with Mologic. “What we’re counting on”, he notes, “is that Mologic can apply their processes to the INSPECTR methodology.”
Sherlock Biosciences’ INSPECTR (Internal Splint-Pairing Expression Cassette Translation Reaction) platform uses cell-free systems as programmable molecular diagnostic devices. INSPECTR can be programmed to distinguish targets based on a single nucleotide. “Our INSPECTR platform was designed to be the very first low-cost, rapid, instrument-free molecular diagnostic system to truly address diagnostic needs where solutions do not exist today, especially in low-resource and home settings,” said Dhanda.
By leveraging the core technologies of Sherlock and Mologic, notes Mark Davis, Mologic’s CEO and Co-Founder, they hope to create extremely sensitive diagnostic tests that produce results with unprecedented speed, without requiring instrumentation, thermal amplification or electricity.