Hi everyone. I wanted to give my preliminary thoughts after reading both of the Kraig Labs patent apps that were published today (1/20/2020) by the US Patent and Trademark office.
The first patent app is entitled:
“Synthesis of Non-Native Proteins in Bombyx Mori by Modifying Sericin Expression”
This patent is absolutely brilliant because it is utilizing a process that normal sericulture views as waste.
In normal sericulture, the silkworm produces sericin that is coated on the outside of the the silk. This protein is undesirable in the silk making processed so in the normal silk making process, cocoons are soaked in hot water until the sericin dissolves, and the cocoon can then spin freely. What’s left, is a sericin rich water that is normally discarded.
What Kraig Labs has wisely done is to replace the sericin gene with a non-native protein target gene. This way, during the normal silk making process, the byproduct isn’t a sericin rich water, it is a bath filled with high concentrations of a target protein.
Here are some of the proteins they have targeted as examples (some of you might remember me suggesting in the past that some of these would be good targets):
Scleroproteins (ie. collagen, elastin, fibrin, keratin): These proteins are used in a lot of industries, but maybe most notably in the cosmetic industry.
Proinsulin: Proinsulin (which eventually matures into insulin) is a target I’ve been bringing up for a long time, but it is nice to see it confirmed in this patent app. This industry is massive, it generates $10’s of billions a year in revenue. If Kraig Labs can produce insulin, or other therapeutic proteins, for cheaper than the current method (microbial protein production), than they become a buyout target for any big pharma company. And remember, this would be a by-product of their sericulture process.
Human Growth Hormones: Anyone can look up the economics of producing HGH, but the bottom line is that its about a $4 billion dollar business.
Human Interferons: I won’t go too far into details because this field is so vast, but in essence these are how a lot of cells communicate with each other in the body.
Factor XIII: I don’t know why I was so surprised to see this in the patent app, but it totally makes sense. This is the enzyme that people, who suffer from Hemophilia A, genetically lack. The current standard of treatment for people who have severe forms of this disease are required to inject synthetic versions (Enzyme Replacement Therapy) of Factor VIII up to 2-3 times a week. If you follow biotech companies like Sangamo (partnered with Pfizer), or Biomarin, than you’ve probably seen the battle thats playing out regarding Hemophilia A, Factor VIII, and other treatments. It is a cash cow for these companies.
The above were only the examples that were available in this patent app, but it has confirmed what some of us have suspected for a while: Kraig Labs is creating a wholly differentiated protein production platform that is highly efficient. This could put a lot of microbial protein producers out of business (i.e., Spiber, Bolt Threads, Amsilk, and even other platforms).
This is EXACTLY how you onshore sericulture back to developed countries. Kraig Labs has created a way to make a by-product that might even be more valuable than the target product (i.e. spider silk fibers). Weight for weight, sericin is about a third of the cocoon. So theoretically, for every 2 tonnes of finish spider silk product, you could produce 1 ton of the target protein (Kraig Labs is knocking out all three sericin genes so no sericin will be produced if not desired).
This is an incredible way to add value to the system, and it’s a complete shake-up of the sericulture industry. This innovation, coupled with the non-mulberry diet transgenic silkworms is how sericulture will easily be profitable in countries with higher labor wages.
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PART 2
The second patent app published today (1/20/2020) might be even more exciting. It is titled:
“Synthesis of High Molecular Weight Proteins Using Inteins”
They were very clever to not disclose the final version of this title when it was first presented to us in the S-1/A filings a couple years ago. Specifically, they left out the term “Inteins”. I assume they did this to keep their cards as close to their vest as long as possible until they absolutely needed to disclose it.
Inteins are pretty amazing and scientists are only now starting to scratch the surface with what they can do. In essence, they can be used to couple two proteins together, and then automatically excise themselves from the protein structure. A lot of work in other fields is to use them for the timing of drug delivery.
Kraig Labs, however, is using them to make their already high molecular weight spider silk proteins, EVEN LARGER!
And not by just double or triple, but by basically as many as they want (I’m sure there’s a theoretical or metabolic limit for the organism). They are doing this by cutting these inteins in half and adding them as couplings at the ends of each of their proteins. These inteins seek each other out, bind, and then remove themselves from the protein chain. And since silks are what are considered fibrous proteins (as opposed to globular, disordered, or membrane type proteins), they can keep coupling together as long as the inteins keep locating each other. This could quickly turn a 500 kDa protein into 1000, 1500, 2000 kDa or more.. The company doesn’t have to disclose their limits so who knows what they are.
This is an incredible breakthrough that will have direct correlation with the mechanical properties of the recombinant silk. This could make many different fibers obsolete, even Aramids (kevlar) and UHMWPEs like dyneema and Spectra because Kraig Labs can decide how many (if any) strength or flexibility motifs they want to include in their final sequences.
But probably the best part of this was how the patent app also covers anyone who tries to do this with the microbial protein production process. Like I’ve said before, companies like Spiber, Bolt Threads, and Amsilk don’t use a proprietary process to make proteins. So now, Kraig Labs gives them a death blow to any process they might think to use inteins for microbeial produced proteins. I’m guessing this is why Kraig didn’t disclose that they were using these amazing molecules. Those microbial protein producing companies still wouldn’t have had a chance for many reasons (most notably cost and low production yields), but this is the dagger in the heart. Bolt Threads has already recognized this, hence their public admittance that mycelium leather is their sole focus. But for the other goo guys, this might be the straw that breaks their back.
All-in-all, there are a lot of great things to be gleaned from these 2 patent apps. I’ll be spending a lot more time on them but I wanted to give you guys my initial thoughts.
These are VERY exciting times for Kraig Labs. They really are building a future in their laboratory.
