A pre-print in Nature explores the combination of CRISPR-ENHANCE technology with a paper-based COVID-19 RNA test to detect targets like HIV, HCV, and prostate cancer.

Before diving into the details, here's how one of the authors describes their findings:

These researchers have previously created a home-based test for coronavirus using the CRISPR-ENHANCE technology.

Overview

They used engineered crRNA (CRISPR RNA) that enhances trans-cleavage activity of Cas12a to amplify nucleic acid detection.

Let's break that down.

CRISPR RNA contains variable targeting sequences, and is the RNA fragment that comes from the spacer sequences snipped by the bacteria before. tracrRNA is a gene in the CRISPR system that activates this CRISPR RNA, and in combination creates the gRNA (guide RNA).

Trans-cleavage refers to recombination involving sites in trans (on seperate molecules), as opposed to in cis (on the same DNA molecule).

Recombination refers to attaching segments of DNA together that normally wouldn't be attached.

As we explore in our article on Cas1 to Cas14, Cas12a is a "cautious editor" that uses crRNA to identify matching DNA that it binds and cuts. Unlike Cas9, after Cas12 finds its target, it also starts cutting nearby single-stranded DNA.

Cas12a is a strong tool for detecting tiny amounts of target DNA in a mixture, and is potentially more precise than Cas9.

Why This Matters

Current tests for viruses like HIV will either check for antibodies in the blood, or do a nucleic acid test (testing for the DNA or RNA of the infection directly).

Rapid and accurate identification is obviously crucial, but diagnosis remains a challenge, especially in resource-limited areas.

Therefore, CRISPR-based methods that can provide robust, accurate, and fast diagnosis would be highly valuable.

As mentioned above, CRISPR Cas orthologues like Cas12a have nonspecific catalytic activities that can be used for nucleic acid detection, such as to produce a fluorescent signal by degrading a labeled nucleic acid.

In combination with lateral flow strips, the hope is that we'll have far better diagnostic tests for viruses like HIV.

In an earlier article, we explored pandemics in the last century:

Name Time Deaths Spanish Flu 1918-1919 40-50M Asian Flu 1957-1958 1.1M Hong Kong Flu 1968-1970 1M HIV/AIDS 1981-present 25-35M Swine Flu 2009-2010 200,000 SARS 2002-2003 770 Ebola 2014-2016 11,000 MERS 2015-present 850 COVID-19 2019-present 15,500 (as of Mar 24, 2020)

As you can see, while the world's attention is now squarely on COVID-19, other viruses have far higher death tolls, which faster and more efficient diagnostics could help mitigate.