Global demand for diagnostic testing has risen sharply during the coronavirus pandemic. Efforts are under way by some biotechnology companies to adapt CRISPR, a genome-editing technology, to test for the novel coronavirus Sars-Cov-2, which is the virus that causes Covid-19.

What is CRISPR?

CRISPR is a tool for genome-editing. CRISPR stands for ‘clustered regulatory interspaced short palindromic repeats’. This technology has the ability to recognise specific genetic sequences and cut them.

Recently, researchers have also discovered CRISPR’s potential role in diagnostics. Several organisations are currently working to innovate in this area. Microbiologist Feng Zhang and others have developed a research protocol. This protocol may help to inform the development of CRISPR-based diagnostics for severe acute respiratory syndrome coronavirus-2 (‘Sars-Cov-2’). Sars-Cov-2 is the name given to the 2019 novel coronavirus. Covid-19 is the name given to the disease associated with the virus. Sars-Cov-2 has not previously been identified in humans.

The research protocol provides a framework for establishing a SHERLOCK-based test. SHERLOCK is a CRISPR-based technology that stands for ‘specific high sensitivity enzymatic reporter unlocking’. SHERLOCK checks for the presence of certain nucleic acid sequences, such as ribonucleic acid (‘RNA’). Sars-Cov-2 is a strain of RNA virus.

A biotechnology company in California, Mammoth Biosciences, is working to validate a CRISPR-based diagnostic tool called DETECTR. This tool identifies specific nucleic acids in samples that are “indicative of disease”. Mammoth Biosciences states it has reconfigured its DETECTR technology to “rapidly and accurately” detect Sars-Cov-2.

Institutions such as the Broad Institute of the Massachusetts Institute of Technology (MIT) and Harvard, and the McGovern Institute for Brain Research at MIT, have also committed to sharing information that may help to support the development of potential diagnostics. 

Current coronavirus testing

There are two main types of test for the novel coronavirus Sars-Cov-2: an antigen test and an antibody test.

An antigen test identifies active infection. It does this by detecting the presence (or absence) of an antigen. An antigen is a structure within a virus that triggers the immune system’s response to fight off infection. These tests detect antigens before the body has created antibodies.

An antibody test determines if an individual has been infected in the past by searching for an immune response (ie to see if the individual has developed antibodies).

In the UK, NHS England has published guidance about the preferred method for conducting antigen tests. The method involves analysing viral genetic material taken from nose and throat swabs. A reverse transcription polymerase chain reaction (‘RT-PCR’) is the test used. This is a type of antigen test.

What is the international response to testing?

The international response to testing is varied. This is because of differences in regulations and readiness.

The World Health Organisation recently called for health agencies across the world to prioritise diagnostic testing. As part of this effort, NHS England’s standard operating procedure (‘SOP’) for Covid-19 virus testing asked pathology networks to identify hub laboratories to lead on this work. The SOP states that the aim is for each NHS hub laboratory to provide a minimum capacity of 500 tests per day, seven days per week. This figure is in addition to the testing provided by Public Health England laboratories and forms part of the government’s 100,000 tests-a-day target from the recently released five-point plan.

The development of an antibody test is also being prioritised by governments, including the UK. The UK Government said that the test could identify those who have had the virus and are now immune. Some healthcare professionals state that antibody tests take longer to create than antigen tests. Dr James Gill, a clinical lecturer at Warwick Medical School, said that the reason for this is because antibody tests have to be produced from scratch. Dr Gill said:

For the antibody test, [you have] to physically get patient blood, find the antibodies in that blood […], create a reproducible antibody in the lab, and then create a reagent test that will react in the presence of that antibody[…] which can [then] be read by health teams.

As a result, the antibody test is far superior, but [requires] creating something from scratch whereas the PCR test is a small addition to an existing test.

What are the next steps for testing?

The UK Government’s five-point plan (‘the plan’) aims to carry out 100,000 coronavirus tests a day (£), in England, by the end of April 2020. This includes NHS swab testing and commercial swab testing. The plan also refers to the introduction of antibody tests to check whether people have had the virus.

This announcement follows increased criticism in the government’s testing regime, particularly in relation to the testing on frontline NHS staff. The Health Secretary, Matt Hancock, said that the government wants to buy 17.5 million antibody tests, subject to them being effective. However, the reliability of the antibody tests has been called into question. Mr Hancock recently said that the antibody tests are not yet “good enough”. The UK Government is looking to recoup money spent on tests ordered from China. This follows an Oxford University trial that found the tests to be unreliable.

Companies are continuing to develop other testing technologies such as CRISPR for potential future diagnostic use.

In the UK, the Government and scientific community have backed the formation of a Covid-19 Genomics UK Consortium. The consortium, armed with a £20 million investment, aims to use whole genome sequencing to determine how Covid-19 spreads. The consortium comprises of the NHS, public health agencies and academic institutions, amongst others.

Further briefings on the novel coronavirus can be found on the House of Lords Library website.

Image by Chokniti Khongchum from Pixabay.