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Principal Investigator: Changchun Liu
Organization: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
Fiscal Year: 2024
Award: $505,996
Funding agency: National Cancer Institute
Abstract
Cervical cancer is among the leading causes of cancer death in women worldwide, especially in low- and middle-
income countries (LMICs). High-risk human papillomaviruses (HPV) are the main causative agents of cervical
cancer and its precursor lesions; therefore, the World Health Organization (WHO) has recommended HPV DNA
testing for cervical cancer screening in LMICs. Although polymerase chain reaction (PCR) methods have been
widely used for HPV DNA detection, they are restricted to centralized clinical laboratories due to the need for
labor-intensive procedures and expensive equipment. Here, we propose to develop a simple, rapid, highly
sensitive, and specific CRISPR-on-paper diagnostic platform to simultaneously detect multiple high-risk HPV
genotypes for cervical cancer screening at the point of care. This innovative diagnostic system is based on our
recently developed all-in-one dual CRISPR-Cas12a (AIOD-CRISPR) assay, which combines the simplicity and
high sensitivity of isothermal nucleic acid amplification with the high specificity of CRISPR detection. To develop
a low-cost, multiplexed molecular detection technology, we will incorporate the AIOD-CRISPR assay into a
paper-based microfluidics platform. To eliminate the need for complex electronic instruments, we will take
advantage of an exothermic reaction to generate chemical heat for the CRISPR-on-paper system by using a
disposable hand warmer, thus enabling instrument-free cervical cancer screening. The detection results can be
read by the naked eye or reported by a programmed smartphone without the need for an expensive optical
detector. We will rigorously evaluate and validate the clinical applications of our CRISPR-on-paper diagnostic
system by testing clinical samples in collaboration with clinicians and healthcare workers in UConn Health and
Zambia. If successful, the proposed project has an important impact on global health by providing a simple,
affordable, and sensitive method for rapid screening of cervical cancer in resource-poor settings. As a platform
technology, the proposed CRISPR-on-paper diagnostic system can be easily adapted to detect other emerging
pathogens.
Terms: <Acetic Acids><Address><Air><Android App><Android Application><Assay><Bio-Informatics><Bioassay><Bioinformatics><Biological Assay><COVID detection><COVID-19 detection><COVID19 detection><CRISPR><CRISPR/Cas system><Cancer Cause><Cancer Etiology><Cell Phone><Cell Phone Application><Cell phone App><Cellular Phone><Cellular Phone App><Cellular Phone Application><Cellular Telephone><Cervical Cancer><Cervical Cancer Screening><Cervix Cancer><Cessation of life><Chemicals><Clinical><Clinical Sensitivity><Clustered Regularly Interspaced Short Palindromic Repeats><Collaborations><Comment><Commentary><Complex><Cytology><DNA><Data><Death><Deoxyribonucleic Acid><Detection><Devices><Editorial Comment><Electronics><Engineering><Equipment><Eye><Eyeball><Feedback><Food and Drug Administration><Funding><Genotype><HPV><HPV detection><HPV infection><HPV screening><HPV-High Risk><Hand><Health><Health Care Providers><Health Personnel><Healthcare Providers><Healthcare worker><High Risk Oncogenic HPV><High risk HPV><High risk Human Papillomavirus><High risk Human papilloma virus><Human Papilloma Virus><Human Papilloma Virus detection><Human Papilloma Virus screening><Human Papillomavirus><Human papilloma virus infection><Human papillomavirus infection><Image><Infectious Diseases / Laboratory><Infectious Diseases Research><Infectious Human Wart Virus><Interdisciplinary Research><Interdisciplinary Study><LMIC><Laboratories><Lesion><Low-resource area><Low-resource community><Low-resource environment><Low-resource region><Low-resource setting><Malignant Cervical Neoplasm><Malignant Cervical Tumor><Malignant Neoplasm of the Cervix><Malignant Tumor of the Cervix><Malignant Tumor of the Cervix Uteri><Malignant Uterine Cervix Neoplasm><Malignant Uterine Cervix Tumor><Malignant neoplasm of cervix uteri><Methods><Microfluidic Device><Microfluidic Lab-On-A-Chip><Microfluidic Microchips><Microfluidics><Mobile Phones><Molecular><Multidisciplinary Collaboration><Multidisciplinary Research><Non-Polyadenylated RNA><Northern Rhodesia><Nucleic Acids><Oncologist><Optics><Paper><Performance><Polymerase Chain Reaction><Printing><Procedures><Process><Published Comment><RNA><RNA Gene Products><Reaction><Recommendation><Reporting><Reproducibility><Research Resources><Resource-constrained area><Resource-constrained community><Resource-constrained environment><Resource-constrained region><Resource-constrained setting><Resource-limited area><Resource-limited community><Resource-limited environment><Resource-limited region><Resource-limited setting><Resource-poor area><Resource-poor community><Resource-poor environment><Resource-poor region><Resource-poor setting><Resources><Ribonucleic Acid><SARS-CoV-2 detection><Sampling><Sensitivity and Specificity><Services><Smart Phone App><Smart Phone Application><Smartphone App><Specificity><Speed><Swab><System><Technology><Temperature><Test Result><Testing><Time><Training><USFDA><United States Food and Drug Administration><Uterine Cervix Cancer><Viewpoint><Virus><Visual><Waxes><Women's mortality><World Health Organization><Zambia><anti-cancer research><burden of disease><burden of illness><cancer research><cell phone based app><cervical cancer early detection><cervical screening><chronic infection><clinical applicability><clinical application><coronavirus detection><coronavirus disease 2019 detection><coronavirus disease detection><cost><death among females><death among women><death in females><death in women><death rate among women><death rate in women><design><designing><detect COVID><detect COVID-19><detect COVID19><detect SARS-CoV-2><detect coronavirus><detect coronavirus disease><detect severe acute respiratory syndrome coronavirus 2><detection assay><detection method><detection procedure><detection sensitivity><detection technique><detector><diagnostic platform><diagnostic system><disease burden><electronic><electronic device><emerging pathogen><experience><female death><female mortality><global health><hands><health care personnel><health care worker><health provider><health training><health workforce><healthcare personnel><high risk><iOS app><iOS application><iPhone><iPhone App><iPhone Application><imaging><industrial partnership><industry partner><industry partnership><innovate><innovation><innovative><instrument><internal control><low and middle-income countries><medical personnel><microfluidic chip><mobile phone app><mortality among females><mortality among women><mortality in females><mortality in women><multiplex detection><new pathogen><novel><novel pathogen><optical><persistent infection><point of care><point-of-care diagnostics><portability><precancer cervical detection><rapid method><rapid technique><severe acute respiratory syndrome coronavirus 2 detection><smart phone><smartphone><smartphone application><smartphone based app><smartphone based application><technology platform><technology system><treatment provider><wart virus><women's death><women's death rate><µfluidic>