Description
Made available in DSpace on 2018-11-26T16:01:08Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-04-27
HHMI
Broad Institute Chemical Biology and Therapeutics Science Shark Tank
NIH
Defense Advanced Research Projects Agency
Paul and Daisy Soros fellowship
NIH National Institute of Allergy and Infectious Diseases
New York Stem Cell foundation
Allen foundation
Vallee foundation
Tan-Yang Center at MIT
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Mitigating global infectious disease requires diagnostic tools that are sensitive, specific, and rapidly field deployable. In this study, we demonstrate that the Cas13-based SHERLOCK (specific high-sensitivity enzymatic reporter unlocking) platform can detect Zika virus (ZIKV) and dengue virus (DENV) in patient samples at concentrations as low as 1 copy per microliter. We developed HUDSON (heating unextracted diagnostic samples to obliterate nucleases), a protocol that pairs with SHERLOCK for viral detection directly from bodily fluids, enabling instrument-free DENVdetection directly from patient samples in <2 hours. We further demonstrate that SHERLOCK can distinguish the four DENV serotypes, as well as region-specific strains of ZIKV from the 2015-2016 pandemic. Finally, we report the rapid (<1 week) design and testing of instrument-free assays to detect clinically relevant viral single-nucleotide polymorphisms.
Broad Inst Massachusetts Inst Technol MIT & Harva, Cambridge, MA 02142 USA
Harvard Univ, Dept Organismal & Evolutionary Biol, Ctr Syst Biol, Cambridge, MA 02138 USA
Harvard Med Sch, Div Med Sci, PhD Program Virol, Boston, MA 02115 USA
Harvard Med Sch, Dept Syst Biol, Boston, MA 02115 USA
MIT, McGovern Inst Brain Res, Cambridge, MA 02139 USA
MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA
MIT, Dept Biol Engn, Cambridge, MA 02139 USA
MIT, Dept Hlth Sci & Technol, Cambridge, MA 02139 USA
MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA
MIT, Inst Med Engn & Sci, Cambridge, MA 02139 USA
Florida Gulf Coast Univ, Dept Biol Sci, Ft Myers, FL 33965 USA
Univ Nacl Autonoma Honduras, Inst Invest Microbiol, Ctr Invest Genet, Tegucigalpa, Honduras
Harvard Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA
Sao Paulo State Univ, Sch Pharmaceut Sci, Araraquara Lab Publ Hlth, Sao Paulo, Brazil
Fac Med Sao Jose do Rio Preto, Lab Pesquisas Virol, Sao Paulo, Brazil
Mt Sinai Sch Med, Dept Med, New York, NY 10029 USA
Harvard Med Sch, Dept Microbiol & Immunobiol, Boston, MA 02115 USA
HHMI, Chevy Chase, MD 20815 USA
Sao Paulo State Univ, Sch Pharmaceut Sci, Araraquara Lab Publ Hlth, Sao Paulo, Brazil
NIH: U19AI110818
NIH: F30 NRSA 1F30-CA210382
NIH: AI 100190
NIH: 1R01-HG009761
NIH: 1R01-MH110049
NIH: 1DP1-HL141201
Defense Advanced Research Projects Agency: D18AC00006
NIH National Institute of Allergy and Infectious Diseases: R01AI099210
FAPESP: 13/21719-3
