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I'm hoping my reply will be a contrarian indicator, as it was with the last survey I answered.
No offense intended toward the religious or non. I simply put great in quotations because those religions which have the most believers are often referred to as the great ones, meaning major. I suppose someone has counted the true number of religions in the world with believers that number more than one, but suffice it to say there are plenty.
"addressing the religious dimension of biotech fanaticism."
I saw it. Personally, I have been fascinated for a long time with a twist of the same words, namely the biotech dimension of religious fanaticism. Its gonna be an amusing day sometime in the future when the most zealous of some of the world's "great" religions find that some shared bits of genotype contribute a predisposition to the intensity of their assorted beliefs (opinions).
I can't state anything factually about their capabilities, but I would assume that they have such a system in place.
I can see GTCB keeping their plate full just with the system they already employ. There are going to be many hundreds of proteins in need of production means in the future.
There are avian patents, but there are also ways engineer around those patents that could not be licensed. So, there is nothing to prevent them from going that route in the future should they so choose. They have dabbled in the past, but before the advent of the current systems.
There are some potential advantages that I see for chickens in the long term, but i still feel that there is more than enough room for all.
1)Without going into details with figures, I can assure you that on a per gram basis, chickens will provide a significant savings over goats. This is taking into account land and waste management, feed conversion, housing, animal and product handling, purification, the whole shebang.
2)The scale up time from founder to production is faster with chickens. Six month generation time so less than two years from mosaic founder through hemizygous generation and on to full homozygotes. Furthermore, with artifical insemination, a single founder rooster can be used to inseminate 20 or so hens per day in about one man hour of work.
3)While every protein is a case by case basis as we have discussed, there are many proteins that cannot be produced in mammals because they are potent cytokines or such that with a slightly leaky system can prove lethal to mammalian physiology.
That's a close up of the Virgina coat of arms!
I do know how to "milk" them.
Your herd might also be a herd of fruit bats. that would change matters.
The sentence did say "commercial production," which is down the road a piece from evaluation of founders.
The malaria vaccine is a tough nut to crack. The proteins from the parasite that are targeted change at an evolutionarily amazing rate, which means the vaccine you make today might not work next month. Nobody wants to make a vaccine that does not have staying power.
Didn't even get as far as the quiz. : )
WAG on my part... overexpression of a milk specific promoter could indeed induce male lactation. That said, I still find the "practically" irelevant, 'cuz who in their right mind would bother hooking any of the males up to the milking machine?
yeah... and how many dairy farmers do you know who keep as many bulls around as cows?
That goes down in the academic drivel silly ass argument category.
And my favorite...
http://www.springerlink.com/content/m186560361278705/
I haven't read the milk patents in some time, but there are a couple of things to consider.
1) Do the GTCB patents cover production in milk using all available promoters, or are they still limited?
2) If a party such as Velander can demonstrate knowledge and use of such production means before the patent was applied for, they have freedom to operate in most cases.
3) Up to 300 liters a year from a giant hungry sow is not a whole lot of milk.
I can't imagine VRA ever getting a partner for the avian stuff. Too much corporate baggage. Why make a deal when you can just wait for them to go under instead? I do expect to see one of the privately held entities on this side of the pond do well.
We're all in agreement about it being good. I only threw the bad hire comment in half jokingly. My main point was that the company has been aware of the need to fill these important positions for a long time, and has been taking their time searching for the correct people. It did not just occur to them that they should start looking.
Don't get too worked up about new job postings. While they may be new to the web site, I believe head hunters have been aware of the same positions for quite some time. Its all good, unless they make a bad hire. : )
The majority of the IP was either trade secret or assimilations of licensed technologies. The decision to go that route was prompted by the cost and length of time it took to get the initial promoter patent issued. That patent, I believe, reverted to Michigan State where it was developed, and then licensed exclusively to the inventor and founder of Geneworks. The vectors were licensed from Cellgenesys. I assume the birds are long gone, including a small (at the time) flock of birds producing a multi-billion dollar off-patent product.
I didn't want to retire, anyway. : )
Hmmm... just got a bitter taste to my coffee. : )
We were a full year ahead of Roslin/VRA on the science front, and way further than that with facilities, but the well went dry, and nobody would fill it up.
"simplifying the organization structure of R&D" means abandoning my town, leaving a 177 acre facility vacant and well over 1000 researchers (2400 statewide)without jobs.
Okay, that was funny. It was gonna be Used to make chickens, but apparently that was one character too many. I should have stuck with stuffishard.
Every protein is a new case.
The chicken folk like to wave the glycosylation flag, and it is a good flag, but has no army behind it yet. Until someone demonstrates publicly that a chicken produced version of a particular protein has better activity than that from a goat, its just a flag.
Perhaps, but I have not seen that to be the case in any proteins I have worked with, or reported by others. Just as with glycosylation issues, every protein is a case by case matter.
Purification schemes are actually pretty simple with egg white, because while the protein concentration is quite high, the number of unique proteins is very, very small compared to the mileau found in other media.
The short answer is time.
GTCB and Pharming have been around a lot longer than any of the serious avian endeavors, which have been at it for about ten years. VRA doesn't count, because they are just throwing money at Roslin in hopes of slavation.
Chickens had some technical hurdles to overcome. Unlike mammals or fish or everything else, the chicken egg does not have a single pronucleus that you can inject. It has many, only one of which ends up being the correct one, so generating the initial mosaic transgenic is more of a numbers game. The primary obstacle however was finding a delivery system that would both 1) get the DNA of interest into the genome, and 2) do so in a way in which it was not "silenced."
Many genomes have ways of recognizing foriegn DNA and preventing any genes therein from expressing themselves. Lentiviruses were the ticket, and this has only been known for about 5 years.
The science itself is not scrambled.
If you run the numbers on cost, taking in to account feed conversion, space requirements, purification schemes, all that stuff, chickens come up significantly cheaper than the goats or cows.
As for the "likely have advantages" comment. This is old news referring to a paper by Raju et al that demonstrates that chickens glycosylate their proteins with patterns more similar to humans than many other species do, including goats. Specifically, it is a matter of NGNA vs NANA side chains.
I'm a believer in the technology, having spent many years working in the field for a now defunct competitor of VRA.
I've been expecting that press release for about a year. Unfortunately for Dr. Sang and Roslin, they are hooked up with a disaster of a company. While their drugs may be 8-10 years down the road, I expect to see marketable products sooner in this country.
Used to go back and forth with Svarten about the birdies on the yahoo board back in the last millenium. : ) Wheels of progress and all that.
Geneworks, which has been out of existence for a little over a year. I'd never admit it if it had been VRA. I don't have a premium membership, so if you'd like to ask me more, feel free to use regular email... loechel4@aol.com
While many an academic loves the challenge of adding or removing the appropriate chain or piece of a chain after the protein has been produced, it wreaks havoc on a business plan. Nearly all of those procedures are costly, and cut way back on your final yield. More often than not, the decision is "let's not make that one."
I spent a lot of time thinking about this when I was in the chicken business. : )
"orders of magnitude" sounds good, but is no longer the case. I believe the difference to be less than one order of magnitude at this time. I'll dig around for some numbers in my spare time.
The key in my mind will be the mABs because the huge doses required compared to something like EPO or NESP. as more of these pass through trials, bioreactor capacity should once again become an issue. Interestingly enough, as huge a market as EPO is responsible for, the world's supply is still produced in roller bottles.
What you are proposing would be significant, but represents an enormous amount of work. Point mutations and multiple nuclear transfers would be simple, cheaper, and less time-consuming. Beyond the initial development of said strains, you would still need multiple generations of cross just to get back to the homozygous background you created.
On top of this, such changes to the host animal would have an impact on, at least, the majority of proteins in milk, which in turn could lead to major hassles in purification schemes.
I don't really think that would do much. It is commonplace to fiddle with glycosylation sites, usually by altering the piece of DNA that gets introduced into the would-be transgenic, not the glycosylation capabilities of the goats themselves. So, while you end up with different lines of goat that express a specific protein with different glycosylation states, this is not any advancement over standard expression platforms which already do the same.
Any time you change platforms you jeopardize previous efforts, at least in terms of time and resources spent. As long as such a change is made prior to the initiation of any trials, its not a huge deal.
TNFR superfamily, of which cd137 is a member, is a busy field. A quick scan of pubmed for "anti-cd137" shows a lot of activity. I have no idea of how much of that is purely academic, or is affiliated with an outside venture.
My guess is they did feasibility studies with multiple entities, and chose goats over bunnies. I doubt the bunnies will be further involved.
I believe their control of glycosylation is actually fairly limited. I haven't read the text of this patent yet, but what I assume at this point is that they can control via minor sequence variations whether a glycosylation site is present, or not. Once a site is present, they cannot control the types of chains that are attached to the protein. Variants at that level can be recognized and purified, but not preferentially generated.
All of this is good though. Just look at Amgen, where a minor change to EPO resulted in NESP, and improved product in terms of performance, not to mention patent protected just in time for the EPO patents to expire.