Limitations of Using Transgenic Goats to Produce Spider Silk

Original paragraph

While making larger quantities of artificial spider silk is already a reality, getting it to a commercially viable level, at which vast amounts can be consistently produced, is not.

The difficulty lies in finding the right gene to code for the right type of silk protein (each spider makes several silks, with different tensile and elastic properties) and in finding the most efficient way to get other organisms to make a lot of it, whether goats, plants or tankfuls of E. coli.

Source
Torres, Phil. "Spiders and Transgenic Goats Lead to New €˜silk Road | Al Jazeera America." Spiders and Transgenic Goats Lead to New €˜silk Road | Al Jazeera America. N.p., 2 May 2014. Web. 17 Oct. 2014. <http://america.aljazeera.com/watch/shows/techknow/articles/2014/5/1/spiders-and-transgenicgoatsleadtonewasilkroada.html>.

Original paragraph

The process of transgenic production is only 10-25% efficient in mice and 1-5% in larger mammals. We have discussed the problems of DNA transfer, but we also need to consider the process of IVF itself. IVF is relatively efficient in mice, but not so in larger mammals and in humans the success rate is about 20%. . Current work suggests that it is not a problem with the technique but that larger animals are inherently less efficient with respect to implantation of the embryos with large numbers wasted. Additionally, insertional mutagenesis will kill or disable some of the pups. A number of transgenics are infertile and these will be useless for future breeding programmes, although if cloning becomes more efficient we may be able to propagate these animals. The sex of the embryo is also important in recombinant protein production and foetal sex analysis has been used in the past allowing early abortion of male transgenics, pre-implantation DNA analysis allows sexing of the eggs prior to transfer.

The time and effort involved in producing useful transgenic animals is immense. The larger animals have long gestation periods and mature slowly. Mice provide less of a problem in this respect. It is also financially draining to keep animals that may not be useful. Additionally, if only 1% of the animals are transgenic all the others must be slaughtered. Since they are genetically modified they cannot be used as foodstuff and must be incinerated. Clearly there is scope for the introduction of new more efficient methods that will allow us to be sure that each experiment yields a transgenic animal with the appropriate gene incorporated at a single chosen site in the genome.

PROBLEMS

efficiency - in mice is only 10-25% in terms of DNA incorporation, in cattle, sheep and goats is 1-5%

insertional mutagenesis kills some of the pups

some of the transgenic pups are infertile

they may not be of the right sex for the purpose e.g. milk production

the time and effort involved are huge

in larger animals the gestation times are long and offspring are not sexually mature for a year

if 1/100 sheep born are transgenic the rest will be slaughtered and the carcasses burnt

larger animals only produce 1 or 2 offspring

viruses/bacteria etc

Source

"Transgenic Animals." Journal of Equine Veterinary Science 22.2 (2002): 94. Web. 18 Oct. 2014. <http://www2.wmin.ac.uk/~redwayk/pgcert_DL/molecular_therapeutics/files/Chapter%206.pdf>.

Original paragraph

During a goat transgenic program that took place in Israel from July 1995 to February 1996, Saanen (n = 343) and Nubian x Damascus (n = 378) crossbred goats of mixed ages were used as donors (n = 433) and recipients (n = 288). The effects of season, age, number of surgical procedures, previous hormonal treatments and ovulation rate on the number of microinjectable embryos collected were studied. Likewise, the effects of these parameters on the pregnancy rate as well as the number of embryos transplanted, endogenous progesterone concentrations and exogenous progesterone supplementation were studied in recipient does. Following superovulation with ovine follicle stimulating hormone, 85% of the does responded with 13.6 +/- 5.7 (mean +/- S D) ovulations/doe. Age, month and number of previous hormonal treatments significantly affected the ovulation rate. The average recovery rate was 70%, and it was affected only by the ovulation rate. Pronuclei were visualized in about 30% of the flushed embryos (including unfertilized ova), and those were microinjected with human serum albumin gene construct. About 68% of the injected embryos underwent at least one division during an overnight incubation, and those embryos were transferred, giving about 2.0 transferred embryos per ovulated donor. Of the recipients, 86% responded following synchronization with 3.1 +/- 1.6 (mean +/- S D) ovulations per doe. Breed and month had a significant effect on the ovulation rate. Two or three microinjected embryos were transferred to each recipient, resulting in more than a 40% pregnancy rate during September to November. Lower pregnancy rates were obtained before and after that period. By monitoring plasma progesterone concentrations in the recipients it was found that progesterone concentration was correlated with the ovulation rate. However, the pregnancy rate was not affected by progesterone concentration. During January and February, 30 to 50% of the recipients failed to develop functional corpora lutea (CL) following embryo transfer, which explained the lower pregnancy rate in those months. Of the 86 kids born 4 were transgenic.

Source
Goodwine, E. "Result Filters." National Center for Biotechnology Information. U.S. National Library of Medicine, n.d. Web. 18 Oct. 2014. <http://www.ncbi.nlm.nih.gov/pubmed/16728144>.

Key ideas:

• The difficulty is finding the right gene code in a spider for its dragline silk
• Also finding the most efficient way to make other organisms to produce it
• The offspring goat might not be the right sex for milk production
• The success rate is small - only about 5%

Paraphrasing

There are several limitations of using transgenic goats to produce spider silk. Among them are the difficulty in finding the gene codes and the host organism, several problems that can arise in the offspring and the very small success rate of the process. One of the difficulties lies in finding the right gene code in a spider for its dragline silk. A single spider produces a variety of silk types and finding the right gene that codes for the strongest and most elastic silk is difficult. In addition to that, scientists still do not know what is the most efficient way to make other organisms produce silk. Goats might be the most effective solution to this problem. The next limitation is problems that can arise in the offspring. One of these problems is that the goat produced with the spider transgene might not be right sex for milk production. This is crucial because scientists rely on the milk production as a natural outlet for the silk. If the goat is male, it would be harder to milk than if it were female. The last limitation is the overall small success rate. The results of a transgenic goat program conducted in Israel from July 1995 to February 1996 is that of the 86 kids born, only 4 were transgenic. This gives us about a 5% success rate of an offspring goat having the spider transgene in them. These limitations are the reasons as to why there are not more companies using transgenic goats to produce spider silk. Especially with the example of Nexia Biotechnologies which infamously went bankrupt after successfully using transgenic goats to produce spider silk.