[K23] The development & pilot implementation of a CRISPR-based low-cost point-of-care assay for detecting Neisseria gonorrhoeae and molecular markers of antimicrobial resistance in resource-limited settings
Ente: National Institute of Allergy and Infectious Diseases
Scadenza: 2029-07-31
Importo max: $154,309
Paese: US
Descrizione
Project Summary
Low-resource settings have a high burden of Neisseria gonorrhoeae infection, but insufficient laboratory
infrastructure for diagnostic tests and antimicrobial susceptibility determination, leading to syndromic
management, which misses a high proportion of cases and results in the overuse of antibiotics. Together, those
factors contribute to driving the emergence of antimicrobial resistance (AMR), a global public health threat.
Two novel strategies can combine to address those challenges. First, the use of CRISPR-based technology
permits the development of low-cost, point-of-care (POC) assays, which can be used in resource-limited
settings. Second, determination of molecular resistance markers can facilitate resistance-guided therapy,
thereby reducing the selective pressure towards AMR. The study aims are: 1) develop CRISPR-based assays
for POC determination of resistance to ciprofloxacin and susceptibility to cefixime, 2) multiplex the two
CRISPR-based AMR assays with an existing N. gonorrhoeae detection assay, and 3) evaluate the validity,
feasibility, and acceptability of the POC N. gonorrhoeae and AMR assay among two health centers in
Botswana. The study is based upon preliminary work in the development POC DNA extraction techniques and
a Cas13a-based lateral flow N. gonorrhoeae detection platform. The proposal leverages specimen collected
through a clinical trial via the Massachusetts General Hospital Sexual Health Clinic, as well as longstanding
collaborations in Botswana. This Mentored Patient-Oriented Research Career Development Award (K23)
supports the career development of Dr. Lao-Tzu Allan-Blitz, an Assistant Clinical Professor with experience in
the epidemiology of and novel diagnostic development for sexually transmitted infections (STI) and AMR. The
K23 will support Dr. Allan-Blitz to develop expertise in 1) assay development for POC detection, and 2) assay
implementation and evaluation. To achieve the proposed research and training aims, Dr. Allan-Blitz has
assembled a team of mentors who are world experts. Dr. Landovitz is a leading expert in the translation of
laboratory innovations into field settings, clinical trial design and conduct, and implementation science; he will
serve as primary mentor. Drs. Jacob Lemieux and Pardis Sabeti, leaders in metagenomics, computational
genetics, DNA sequencing, and CRISPR-based assay development, will serve as co-mentors along with Dr.
Shahin Lockman, a renowned implementation science researcher with longstanding collaborations in
Botswana. The proposed research and training aims will leverage strong, longstanding collaborations and the
robust research infrastructure between Dr. Allan-Blitz, his mentorship team and the Botswana Harvard AIDS
Institute Partnership. Finally, the K23 award will advance Dr. Allan-Blitz’s career goal of becoming an expert in
STI assay development and implementation, with a specific focus on low-resource settings, as well as
facilitate his transition
Istituzione: UNIVERSITY OF CALIFORNIA LOS ANGELES
PI: Lao-Tzu Allan-Blitz
Progetto: 7K23AI182453-03
Settori: National Institute of Allergy and Infectious Diseases
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