Thread by @Biotech2k1

The Private Company #CRISPR Report

I am going to build this thread going through the private CRISPR companies. This includes the few that I do know and like. I know there are more out there. I will add them as I discover them and take time to look over their science.

1/ Mammoth Biosciences

This is my top pick of the private companies should they go public. I think they are gearing up for an IPO. The success of the $PRME IPO might bring them to the market quicker.

2/ They have 2 platforms based off CRISPR technology. The first uses CAS enzymes for DNA or RNA as a Diagnostic tool. They take the guide RNA for the sequence they wish to find. They include a reporter strand that matches the DNA sequence they want to find.

3/ The CAS enzyme uses the guide RNA to find the right sequence in the DNA or RNA. Then it activates its nuclease which cuts the DNA or RNA. It will also cut the reporter molecules that are added. This causes them to activate and read out.

4/ They already have commercial Covid test using this type of CRISPR diagnostic reporter tool. The other program they are working on are new CAS enzymes with CAS-Phi and CAS-14. These are dramatically smaller than the older CAS9 enzymes. I call them the CAS-mini.

5/ They don't have any clinical programs for these newer CAS enzymes yet. I would think they would want some kind of clinical pipeline with these assets before going public. I don't think the diagnostics alone makes them as compelling for value.

6/ I believe at their last financing round they were valued around $1 billion. That would be expensive should all they have is diagnostics at the time of the IPO. They would have to have a ton of diagnostic revenues to justify that value.

7/ Overall, I rank them as the best of the private CRISPR companies because they do offer to very diverse platforms with CRISPR based technology with Diagnostic and Therapeutics.

8/ Scribe Therapeutics

They are a private company working with a newly discovered version of the CRISPR CAS enzyme. The original CAS9 and CAS12 were discovered in Strep.

9/ That has led many of these companies to go out and look at other bacteria and organisms to see what CRISPR systems might still be out there. CRISPR CAS-X was discovered in E coli bacteria. I read the paper they published on this enzyme.

10/ It works very much like CAS12 with staggered doubles stranded breaks. It is smaller than the original CAS enzymes at about 1,000 amino acids in length. It even uses a TTCN PAM sequence. This gives us a whole new CAS enzyme for which to build therapies.

11/ They could build this into a base editor, a prime editor or any number of unique combinations. I have not seen any in use published data for this system yet. Its still very early in its discovery phase of development.

12/ I don't think we will see this one come public for a few more years. It has a bunch of work to do yet and generate enough data in at least mice to show investors before it would be ready.

13/ Arbor Biotechnologies

This company is one that I am really excited to talk about as I think they are a CRISPR company of high innovation. Many people focus on the labs like Dr Liu who brought to us technologies like Base Editing and Prime Editing.

14/ Arbor is another company on the cutting edge of new discovery. They have sequenced the CRISPR from many organisms and identified over 60 CAS nucleases and over 70 Transposons. They are working on breakthroughs in new ways to do editing.

15/ They are really early in the discovery of these programs. They have been working on several programs that I got to read papers for. The one drawback I saw was I wish they put more of the publications on their Science page for easy to find.

16/ I don't think they will be name we will see going public any time soon, but they do have a pipeline on their website with a first target of Hyperoxaluria. I don't know which CAS enzyme setup they chose for this program if they selected on yet.

17/ I can't wait to see what new editors they come up with. They could do split editors with dimerization, they could do base or prime like editors. I think the combination of CAS nuclease and a transposon is very interesting. They could even get into epigenetic regulation.

18/ Sherlock Biosciences

This company use to be my #2 private pick. It has since changed. It is not because they did anything wrong. They are solely focused on using CRISPR technology for Diagnostics. I find that exciting, but it probably has more limited potential.

19/ They have 2 diagnostic programs. The first works like the one from Mammoth. They use the guide RNA to find the right sequence in the DNA or RNA, then the nuclease will cut and also cut the reporter molecules nearby. This gives a read out.

20/ The other is their INSPECTOR platform which compares two sequences of DNA or RNA. When ever there are changes, a reporter sequence is read out. I am not as up to speed with how this works, but its really fascinating.

21/ The big drawback for Sherlock is they have no editing program with a CAS enzyme or nuclease. That kind of limits the potential of what they could become. I am not sure if they are even looking to go public. I haven't seen them talked about all that much.

22/ That could be for the same reason I lost some interest in them. The real focus for the technology is using it to edit the human genome in a safe and efficient way. There are tons of other diagnostics out there that work just fine.

23/ Incripta

I don't think this company has any aspirations of going public, but I think they are one of the most amazing stories out there. Why are they #5 then? Because they have so much more than just CRISPR.

24/ Their first platform falls into it #TechBio, #CellEnginering, #SynBio and #CRISPR. Yes, they have a machine called the Onyx. It allows users to access their software to develop and design microbes. Then the machine makes the edits to the microbes using the #AI software.

25/ This allows the user to design, test and redesign very efficiently to get the perfectly CRISPR edited microbes for use in whatever therapy or application they are using them for. This is super cool technology that comes close to having a DNA/Microbe printer in the lab.

26/ The other platform they have is their CRISPR MAD-7 enzyme. This was discovered in a bacteria in Madagascar hence the name MAD-7. This is a very good enzyme which they license freely to anyone for a small royalty.

27/ I know a few of my companies have a license with Inscripta for MAD-7 use. This makes this company one of the coolest private companies that will probably never go public. We can hope though.