Amplifying CRISPR: Next-Generation Diagnostics

Abstract

The CRISPR JournalVol. 6, No. 2 EditorialFree AccessAmplifying CRISPR: Next-Generation DiagnosticsRodolphe BarrangouRodolphe BarrangouEditor-in-Chief, The CRISPR Journal.Search for more papers by this authorPublished Online:13 Apr 2023https://doi.org/10.1089/crispr.2023.0004.editorialAboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail Although the path to the clinic of CRISPR-based technologies has focused primarily on therapeutics, the road to most consumers is much more likely to be in the realm of diagnostics. Indeed, CRISPR diagnostic assays are on the way to our homes in the form of test kits and rapid tests enabling the detection of agents responsible for infectious diseases.As we have all observed over the past 3 years, the COVID-19 pandemic has changed our world in many ways. Although large-scale systemic testing is not as en vogue as it once was, advances in CRISPR-based detection are on the rise. Moving forward, we need access to nimble technologies that will monitor and detect the next wave of viruses, wherever and whenever they materialize.The convenient programmability of Cas molecular machines engineered for genome editing, in combination with the specificity of natural CRISPR-Cas systems for adaptive immunity, makes them ideal for diagnostics. Indeed, their exquisite programmability enables the accurate targeting of sequences unique to viruses and bacteria responsible for infectious disease, whereas superior specificity allows the sensitive detection of low levels of human pathogens in small samples.Several platforms have already been developed by commercial entities, building off technologies such as SHERLOCK, DETECTR, and others, using Cas effectors such as Cas12 and Cas13 to detect DNA and RNA, respectively.In this issue of The CRISPR Journal, we feature a collection of CRISPR diagnostic research articles, making up our latest special issue (after our four previous special issues on “The CRISPR Toolbox” (2019), “Human Hereditary Genome Editing” (2019), “CRISPR in China” (2020), and CRISPR's Path to the Clinic (2021).The CRISPR diagnostics collection in this issue illustrates the potential and practical applications of Cas effectors for epidemiological surveillance and detection. On page 99, an international team encompassing groups from Thailand, the United Kingdom, and the United States shows how multiplexed Cas13-based assays can be used for detection of several COVID-19 variants, including delta and omicron. Using a combination of LwaCas13a and PsmCas13b, the authors show how these variants of concern can be detected and discerned in one-pot reactions for point-of-care diagnostics.On page 116, a team from Mexico shows how multiplexed Cas12a guides can be used in parallel for rapid detection of SARS-CoV-2 RNA down to 10 copies in clinical samples. The authors show that this can provide readouts within 25 min for fluorescence readers, or 45 min for lateral flow sticks.Besides the detection of nucleic acid from infectious disease agents, this approach can be used in the context of DNA diagnostics for cancer detection. On page WW, a team from The Netherlands shows how Cas12a can also be used to target cancer-associated mutation hotspots for presymptomatic cancer detection or post-treatment monitoring. There are prospects for cost-effective point-of-care tumor biopsy analysis and opportunities for individualized monitoring of patients with proof of concept provided for melanoma, and breast, mouth, lung, and mouth carcinoma.Likewise, a French group (page 140) shows how oncogenic EGFR rearrangements involved in chronic myeloid leukemia can be detected. The authors show that SHERLOCK sensitivity is superior to the PCR gold standard, opening opportunities for detection of low-level tumor residuals from blood samples.These interesting reports illustrate the power of exploiting CRISPR-based molecular machines for human diagnostics across infectious disease and DNA mutations. Besides access to quick, sensitive, and specific assays, there is a strong upside with regard to affordable point-of-care use with price elasticity implications across governmental health care financial models. Furthermore, in addition to human diagnostics, these technologies hold potential for agricultural deployment across the food supply chain in an ever-expanding global context, as well as environmental monitoring for sustainability applications.We keep putting CRISPR to work. Only time will tell how far and how fast this disruptive technology will reach patients and consumers.FiguresReferencesRelatedDetails Volume 6Issue 2Apr 2023 InformationCopyright 2023, Mary Ann Liebert, Inc., publishersTo cite this article:Rodolphe Barrangou.Amplifying CRISPR: Next-Generation Diagnostics.The CRISPR Journal.Apr 2023.85-85.http://doi.org/10.1089/crispr.2023.0004.editorialPublished in Volume: 6 Issue 2: April 13, 2023PDF download