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Rapid, Low-Cost Detection of Zika Virus Using Programmable Biomolecular Components.
Literature Information
| DOI | 10.1016/j.cell.2016.04.059 |
|---|---|
| PMID | 27160350 |
| Journal | Cell |
| Impact Factor | 42.5 |
| JCR Quartile | Q1 |
| Publication Year | 2016 |
| Times Cited | 505 |
| Keywords | Zika virus, low-cost detection, biomolecular sensors, CRISPR/Cas9, synthetic biology |
| Literature Type | Journal Article, Research Support, Non-U.S. Gov't |
| ISSN | 0092-8674 |
| Pages | 1255-1266 |
| Issue | 165(5) |
| Authors | Keith Pardee, Alexander A Green, Melissa K Takahashi, Dana Braff, Guillaume Lambert, Jeong Wook Lee, Tom Ferrante, Duo Ma, Nina Donghia, Melina Fan, Nichole M Daringer, Irene Bosch, Dawn M Dudley, David H O'Connor, Lee Gehrke, James J Collins |
TL;DR
This study presents a rapid, low-cost diagnostic pipeline for detecting Zika virus RNA using cell-free, paper-based sensors that integrate isothermal amplification and toehold switch RNA sensors, achieving specificity against Dengue virus. The developed platform, which includes a CRISPR/Cas9 module for strain discrimination, demonstrates practical applicability in field settings and showcases the potential of synthetic biology to address urgent global health challenges.
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Zika virus · low-cost detection · biomolecular sensors · CRISPR/Cas9 · synthetic biology
Abstract
The recent Zika virus outbreak highlights the need for low-cost diagnostics that can be rapidly developed for distribution and use in pandemic regions. Here, we report a pipeline for the rapid design, assembly, and validation of cell-free, paper-based sensors for the detection of the Zika virus RNA genome. By linking isothermal RNA amplification to toehold switch RNA sensors, we detect clinically relevant concentrations of Zika virus sequences and demonstrate specificity against closely related Dengue virus sequences. When coupled with a novel CRISPR/Cas9-based module, our sensors can discriminate between viral strains with single-base resolution. We successfully demonstrate a simple, field-ready sample-processing workflow and detect Zika virus from the plasma of a viremic macaque. Our freeze-dried biomolecular platform resolves important practical limitations to the deployment of molecular diagnostics in the field and demonstrates how synthetic biology can be used to develop diagnostic tools for confronting global health crises. PAPERCLIP.
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Primary Questions Addressed
- How can the programmable biomolecular components be adapted for detecting other viral infections beyond Zika?
- What are the limitations of the current paper-based sensors in terms of sensitivity and specificity?
- In what ways can the CRISPR/Cas9-based module be enhanced to improve strain discrimination in other pathogens?
- What are the potential applications of this technology in resource-limited settings outside of Zika virus detection?
- How does the field-ready sample-processing workflow compare to traditional diagnostic methods in terms of efficiency and cost?
Key Findings
Key Insights
Research Background and Objective: The recent outbreak of the Zika virus has underscored the urgent need for effective, low-cost diagnostic tools that can be swiftly developed and deployed, particularly in regions heavily affected by pandemics. The primary objective of this research is to create a rapid, accessible diagnostic solution for detecting Zika virus RNA, leveraging advancements in synthetic biology and biomolecular engineering to facilitate field use.
Main Methods and Findings: The study reports a novel pipeline for the design, assembly, and validation of cell-free, paper-based sensors specifically tailored for Zika virus detection. This method combines isothermal RNA amplification with toehold switch RNA sensors, enabling the detection of clinically relevant concentrations of Zika virus RNA while maintaining specificity against similar viral sequences, particularly those from the Dengue virus. Notably, a CRISPR/Cas9-based module was incorporated to enhance the sensors' ability to differentiate between viral strains at a single-base resolution. The research successfully showcases a straightforward and field-ready sample-processing workflow, demonstrating the practical application of these sensors by detecting Zika virus RNA in the plasma of a viremic macaque.
Core Conclusions: The findings illustrate the effectiveness of the developed paper-based sensors in providing rapid and specific detection of Zika virus RNA, marking a significant advancement in molecular diagnostics. The integration of programmable biomolecular components allows for high specificity and sensitivity, which is crucial for accurate viral detection in clinical settings. The ability to distinguish between closely related viral strains at a single-base level further enhances the utility of this diagnostic tool in epidemiological tracking and outbreak management.
Research Significance and Impact: This research has considerable implications for global health, particularly in the context of emerging viral threats. The low-cost, easy-to-use nature of the diagnostic tool enhances accessibility in regions with limited resources, enabling timely and effective responses to outbreaks. By overcoming practical limitations associated with molecular diagnostics in the field, this work exemplifies the potential of synthetic biology in developing innovative solutions to pressing public health challenges. The successful application of these sensors could pave the way for similar approaches to diagnose other infectious diseases, ultimately contributing to improved disease surveillance and control efforts globally.
Literatures Citing This Work
- Instrument-Free Point-of-Care Molecular Detection of Zika Virus. - Jinzhao Song;Michael G Mauk;Brent A Hackett;Sara Cherry;Haim H Bau;Changchun Liu - Analytical chemistry (2016)
- Cell-Free Mixing of Escherichia coli Crude Extracts to Prototype and Rationally Engineer High-Titer Mevalonate Synthesis. - Quentin M Dudley;Kim C Anderson;Michael C Jewett - ACS synthetic biology (2016)
- An ultrasensitive electrogenerated chemiluminescence-based immunoassay for specific detection of Zika virus. - Dhiraj Acharya;Pradip Bastola;Linda Le;Amber M Paul;Estefania Fernandez;Michael S Diamond;Wujian Miao;Fengwei Bai - Scientific reports (2016)
- New Paradigms for Virus Detection, Surveillance and Control of Zika Virus Vectors in the Settings of Southeast Asia. - Indra Vythilingam;Jamal I-C Sam;Yoke F Chan;Loke T Khaw;Wan Y Wan Sulaiman - Frontiers in microbiology (2016)
- Diagnostics in Ebola Virus Disease in Resource-Rich and Resource-Limited Settings. - Robert J Shorten;Colin S Brown;Michael Jacobs;Simon Rattenbury;Andrew J Simpson;Stephen Mepham - PLoS neglected tropical diseases (2016)
- The growing impact of lyophilized cell-free protein expression systems. - J Porter Hunt;Seung Ook Yang;Kristen M Wilding;Bradley C Bundy - Bioengineered (2017)
- Rapid Detection Strategies for the Global Threat of Zika Virus: Current State, New Hypotheses, and Limitations. - Shruti Shukla;Sung-Yong Hong;Soo Hyun Chung;Myunghee Kim - Frontiers in microbiology (2016)
- Rapid, Affordable and Portable Medium-Throughput Molecular Device for Zika Virus. - Kamfai Chan;Scott C Weaver;Pui-Yan Wong;Sherly Lie;Eryu Wang;Mathilde Guerbois;Siva Praneeth Vayugundla;Season Wong - Scientific reports (2016)
- Point-of-Care Diagnostics: Recent Developments in a Connected Age. - Samiksha Nayak;Nicole R Blumenfeld;Tassaneewan Laksanasopin;Samuel K Sia - Analytical chemistry (2017)
- Future developments in biosensors for field-ready Zika virus diagnostics. - Ariana M Nicolini;Katherine E McCracken;Jeong-Yeol Yoon - Journal of biological engineering (2017)
... (495 more literatures)
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