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Observations #8
A set of ideas and observations from a week’s worth of work analyzing businesses and technologies.
Everlywell and Scanwell and at home tests
There are countless headlines of new diagnostics tests being developed or approved. This is all great, but how will patients get access. Through hospitals? Quest/LabCorp? At home tests? Their needs to be a CLIA lab in the process of testing patients. Companies like Everlywell and Scanwell have introduced interesting tests for COVID-19 but have not seen the uptake from patients or approval from the FDA. At home tests especially for something like COVID-19 might be a little too early.
An interesting model is being done by Carbon Health to haul a CLIA lab to sites to increase testing accessibility — https://carbonhealth.com/mobile-clinic#click=https://t.co/93pjMYH9Vv
To get people back to work, accessible testing is needed. However, current infrastructure is capable but not coordinated in a way to solve this problem quickly. Are there business models to make COVID-19 diagnostics accessible and build other services around the test like co-location and employer verification?
Ribosome engineering
Engineering restriction enzymes transformed our ability to use DNA for commercial applications.
Engineering polymerases transformed our ability to use RNA similarly.
Engineering ribosomes is moving forward in a way that suggests that the emerging toolkit can have a similar impact that cloning and IVT had on biotechnology. It seems we’re at the stage where technology development is still needed and old business models (i.e. reagents, tools) can be used to validate the idea of engineering a ribosome.
First, what is ribosome engineering? The ribosome is composed of two subunits — large and small and in bacteria, 50S and 30S as well as a 16S rRNA. The ribosome uses this dual subunit structure to recognize a wide set of substrates from mRNAs to tRNAs to bring an amino acid to the amino acids themselves to convert the mRNA code into proteins. This offers a lot of points of contact to add new capabilities to the ribosome:
- Use a different mRNA code
- Recognize a wider set of amino acids and possibly introduce new types of chemical bonds within and between them
- Generate polymers that aren’t proteins
- Rev up the ribosome to produce more protein
- Create orthogonal protein production pathways within the cell
- Playing around with the 16S rRNA sequence to redirect a small proportion of small subunits of the ribosome to translate a different class of mRNAs and sometimes using the rRNA to selectively fuse two subunits
The cutting edge toolkit for ribosome engineering is tethering — https://www.ncbi.nlm.nih.gov/pubmed/26222032?dopt=Abstract The premise is to fuse the rRNAs of the large and subunit to tether them and create an orthogonal ribosome system. With this platform, one could do gain-of-function (GoF) screening to find ribosome variants that do things you want them to do. The hard part is avoiding translation termination and finding the balance between mutating the ribosome and reducing its capacity to make protein. A large bottleneck has been the inability to create a truly orthogonal 50S subunit. Then most tethered ribosome platforms translate proteins a little over half the rate of dissociable equivalents and have lower biogenesis rates. So to bring the power of ribosome engineering to new products:
- Invent an orthogonal large subunit of the ribosome
- Ability to screen for GoF without significantly affecting translation and biogenesis rates
