NCT03342547

Identification of Host Factors of Norovirus Infections in Mini-Gut Model

Status unknown NA Last updated 20 September 2018

What this trial tests

NA trial testing Duodenal biopsy in Gastrointestinal Infection in 20 participants. Status unknown.

Timeline

18 April 2018

Primary endpoint
31 December 2020

31 December 2020

Quick facts

Lead sponsor	Chinese University of Hong Kong
Phase	NA
Status	Status unknown
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	basic science
Enrollment	20
Start date	18 April 2018
Primary completion	31 December 2020
Estimated completion	31 December 2020
Sites	1 location across China

Drugs / interventions tested

• Duodenal biopsy
• Saliva — full drug profile →

Conditions studied

• Gastrointestinal Infection — all drugs for Gastrointestinal Infection →

Sponsor

Chinese University of Hong Kong

Who can join

18 and older, any sex, with Gastrointestinal Infection. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

The primary objective in this study is to establish a list of host cellular proteins that mediate norovirus infection.

Norovirus is one of the most common pathogens attributed to diarrheal diseases from unsafe food. It is also the primary cause of mortality among young children and adults in foodborne infections. Norovirus is not just a foodborne burden. In a recent meta-analysis, norovirus accounts for nearly one-fifth of all causes of (including person-to-person transmission) acute gastroenteritis in both sporadic and outbreak settings and affects all age groups. Undoubtedly, norovirus is of paramount public health concern in both developed and developing countries. Research efforts to better understand norovirus pathobiology will be necessary for targeted intervention.

From Middle East respiratory syndrome coronavirus to Zika virus, efforts to identify host factors important for mediating virus infection has always been a research priority. Such information will shed light on potential therapeutic targets in antiviral intervention. Norovirus virus-host interaction studies have been hampered by the lack of a robust cell culture model in the past 20 years. In 2016, norovirus has finally been successfully cultivated in a stem cell-derived three-dimensional human gut-like structure called enteroid or mini-gut.

In this study, intestinal stem cells will be isolated from duodenal biopsies collected from participants, followed by differentiation into mini-guts. Genome-wide genetic screening for host essential and restrictive factors will be performed on infected mini-guts by knockout CRISPR and gain-of-function CRISPR SAM, respectively. Shortlisted candidates will undergo preliminary functional validation in cell lines. These data will provide insights into potential therapeutic targets against norovirus infection.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. CRISPR-Cas9: A Preclinical and Clinical Perspective for the Treatment of Human Diseases.
   Sharma G, Sharma AR, Bhattacharya M, Lee SS, et al · · 2021 · cited 182× · PMID 33238136 · DOI 10.1016/j.ymthe.2020.09.028
2. <i>In vivo</i> genome editing in animals using AAV-CRISPR system: applications to translational research of human disease.
   Lau CH, Suh Y. · · 2017 · cited 124× · PMID 29333255 · DOI 10.12688/f1000research.11243.1
3. Current trends of clinical trials involving CRISPR/Cas systems.
   Zhang S, Wang Y, Mao D, Wang Y, et al · · 2023 · cited 35× · PMID 38020120 · DOI 10.3389/fmed.2023.1292452
4. The power and the promise of CRISPR/Cas9 genome editing for clinical application with gene therapy.
   Guo N, Liu JB, Li W, Ma YS, et al · · 2022 · cited 32× · PMID 36100322 · DOI 10.1016/j.jare.2021.11.018
5. CRISPR/Cas9 based genome editing for targeted transcriptional control in triple-negative breast cancer.
   Deepak Singh D, Han I, Choi EH, Yadav DK. · · 2021 · cited 28× · PMID 34025931 · DOI 10.1016/j.csbj.2021.04.036
6. Disruptive Technology: CRISPR/Cas-Based Tools and Approaches.
   Patsali P, Kleanthous M, Lederer CW. · · 2019 · cited 19× · PMID 30945167 · DOI 10.1007/s40291-019-00391-4
7. CRISPR CLIP: comprehensive reviews on interventional studies using precision recombinant technologies: clinical landmarks, implications, and prospects.
   Chodnekar SY, Tsetskhladze Z. · · 2024 · cited 1× · PMID 39659430 · DOI 10.1093/oxfimm/iqae013
8. CRISPR-Cas9-mediated therapeutics: Current clinical trials and therapy approval landscape to treat human diseases.
   Chakraborty C, Bhattacharya M, Das A, Agoramoorthy G, et al · · 2026 · PMID 42028170 · DOI 10.1016/j.omtn.2026.102859