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A simple, colour change based at-home diagnostic that is cheap and scalable

B: One to watch

The idea relies on protein complementation technology, which is very well applied in life sciences research. Here we take advantage of camelid nanobodies that have recently been published (https://www.biorxiv.org/content/10.1101/2020.03.26.010165v1) - these nanobodies bind to RBD domain of CoV S protein. Since S protein is a trimer, 2 nanobodies can bind each S trimer. So, by genetically engineering two constructs - one with nanobody fused to one half of the split enzyme, and other nanobody fused to other half - we have a system that will be brought together if and only if virus is present. Using LacZ enzyme for this should theoretically enable detection of 10^4 virions, similar to RT-PCR. At the least, this can be used as a preliminary check before confirmation by RT-PCR.

Have you validated this method, if so, how and what were the results of the validation?

The method is not validated as presented. However, split protein technology is very well established, and I am only repurposing the technology towards Covid19 detection.

How quickly could this be deployed and what are the dependencies?

This will need a couple weeks of R&D to test and optimize the system

What is the likely production volume?

Yeast expressing the constructs is very easy to grow at scale, so this should be easy to mass produce using industrial fermenters at 1000s of litres scale - sufficient to create millions of test daily.

What are the risks and barriers to using this at scale?

No risks that I can foresee. Availability of chemical substrate (Xgal) for the enzyme could be an issue, but it is already mass produced by several industrial suppliers (Sigma Aldrich, ThermoFisher Scientific etc), so I dont think it should be limiting to produce at scale

Who are you already partnering with on this?

No one yet

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Nikolay Zenkin Apr 16, 2020

lacZ is active only as a teramer

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Ganesh Kad Apr 16, 2020

Thanks, had missed thinking about. We could replace LacZ with DHFR, and use a NADP-coupled colourimetric readout, that should be a feasible alternative I think?

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Bev Matthews Apr 19, 2020

Status label added: B

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Bev Matthews Apr 21, 2020

The idea has been progressed to the next milestone.

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Bev Matthews Apr 25, 2020

The idea has been progressed to the next milestone.

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Bev Matthews Apr 25, 2020

Hello Ganesh, our reviewers would like to hear from you when you have completed a validation process. We look forward to hearing from you at that point. Bev

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Tom Jordan Jul 7, 2020

Hi Ganesh, are there any updates you can share with us on this? I see your comment above on validation, nevertheless the team does wanted to know whether you or others had run a validation process specifically with COVID and could share findings.

Kind regards,
Tom
Testing Methods Team

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Tom Jordan Jul 20, 2020

Thanks again for posting this idea Ganesh, we wish you well in progressing and sharing this.

Best wishes,
Tom

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