31 May 2007

The Chicken that lays golden eggs

We have all heard of the fairytale but soon they may longer be just a mystical creature. Researchers at the Roslin Institute have produced genetically modified chickens that lay eggs full of cancer fighting proteins. This research could lead to a faster and cheaper way of manufacturing drugs on a large scale.

Currently, the active ingredients of drugs are made in industrial bioreactors which are time consuming and expensive to set up. An increase in global demand for pharmaceuticals has led researchers to explore more efficient and economical alternatives to standard techniques such as the use of transgenic animals.

A transgenic animal is one that has had external genes incorporated into its genome. In this way, the gene for a protein of a drug of interest can be transferred into the genome of an animal which transmits it to successive generations. The use of chickens offers many advantages. Chickens reproduce quickly, lay lots of eggs and are cheap to look after.

Ovalbumin makes up more than half of the protein in the white of an egg. Researchers have modified the gene that makes ovalbumin so that it produces therapeutic proteins. The proteins are then easily extracted and used in the manufacture of drugs.

The manufacture of drugs created in this way is in its early stages and it will be some time before we see these drugs available on the market. There are ethical issues involving animal welfare and the genetic modification of animals that need to be debated.


Philippa Hall

40113456



Viruses: A Cure for Cancer?

Malignant tumours (tumours with invasive characteristics) or cancer has been an increasing problem in both animal and human health. Recent studies have discovered another weapon to stopping them - the chicken anaemia virus (CAV).

CAV causes both clinical and subclinical diseases in chickens, characterised by anaemia, lymphoid atrophy and immunosuppression. This virus is known to be link with the apoptosis of cells, a form of cell death. The virus contains genes that generate 3 distinct proteins: VP1, VP2 and VP3. The VP3 protein was determined to be responsible for inducing cell apoptosis in chicken mononuclear cells, leading it to be named Apoptin. The good news is that VP3 not only induces apoptosis in chicken mononuclear cells, but also in malignant tumour cells. The ‘special’ ability of the VP3 protein is that it only attacks tumour cells and non-tumour cells, making it an exceptional anti-tumour agent.

Studies have begun investigating the effect of the VP3 gene, which produces the VP3 protein on canine mammary tumour cells. The VP3 gene was introduced into tumour and non-tumour cells via expression vectors (genes constructed containing at least a promoter, transcribed and transcription region) encoded with the VP3 gene of the CAV. The results indeed confirmed VP3 gene’s ‘special’ ability. Therefore, it may be an encouraging agent in treating mammary gland tumours in dogs. Veterinary medicine is not the only area to benefit from this discovery, as it could also lead to a better treatment of human breast cancer.

Primary Source

Lee, JJ., Chen, PB., Yang, SH., Cheng, CH., Chueh, LL., Pang, VF., Hsiao, M., Lin, CT., 2007. Effect of the VP3 gene of chicken anemia virus on canine mammary tumor cells. American Journal of Veterinary Research 68, 411-422. [electronic abstract]

Secondary Sources

Noteborn, MH., 2004. Chicken anemia virus induced apoptosis: underlying molecular mechanisms. Veterinary Microbiology 98, 89-94. [electronic abstract]

Houdebine, L., 2003. Animal Transgenesis and Cloning, edition unknown. John Wiley & Sons Ltd, West Sussex, p.16.

Posted by Sarah Zhang (41426957)

Pharms of the Future

The common chicken may prove to be the next big thing in pharmaceutical production.

Scientists have succeeded in producing transgenic hens that are able to synthesise therapeutic proteins. This may lead to a quicker, easier way of producing anticancer drugs.

Bioreactors (which use bacteria to produce proteins) are currently used, but are expensive and time-consuming so alternatives have been an area of research. Therapeutic proteins are already produced in other transgenic animals (animals containing genes from another species within their genome) such as goats, rabbits and cattle. Using chickens is appealing in that only a 5 month generation time is needed, meaning breeding to produce a large transgenic flock is much quicker than in animals such as goats. Chickens are also cheaper to maintain, and there is the possibility of producing proteins that are toxic to mammalian cells.

The process involves injecting the embryos of newly-laid eggs with viruses that contain the genetic sequences coding for one of two specific proteins (Wayman, 2007). The protein is incorporated into the DNA and results in a transgenic cockerel which is crossed with normal hens to produce transgenic chicks. These chicks go on to pass the proteins into their eggs where it can be collected from the egg white and ultimately used in human drugs.

Importantly, the proteins have been restricted to the oviduct, as the proteins may be harmful to other parts of the chicken. There still needs to be testing for effectiveness in humans, but it mightn’t be too long before eggs become our new drug supplier.

By Julia Smith
41409286


References

Jones, H., (2007) Chicken eggs make human drugs. Cosmos Online.
http://www.cosmosmagazine.com/node/966

Lillico, S., Sherman A., McGrew, M., Robertson, C., Smith, J., Haslam, C., Barnard P., Radcliffe, P., Mitrophanous, K., Elliot E., and Sang H., (2007) Oviduct-specific expression of two therapeutic proteins in transgenic hens. PNAS, February 6, 104:6 p 1771-1776
www.pnas.org/cgi/doi/10.1073/pnas.0610401104

Wayman, E., (2007) Barnyard Pharmaceuticals. Science Now.
http://sciencenow.sciencemag.org/cgi/content/full/2007/116/4

Genetically engineering animal proteins for pharmaceutical benefit

Genetically engineering animal proteins for pharmaceutical benefit

Gene farming of animals in order to produce useful proteins and other pharmaceuticals has been tried and tested on numerous animal species, such as cattle, sheep and pigs. This “gene farming” involves altering an animals DNA or to add additional DNA from another species, which can be achieved by microinjecting a cell (such as a fertilized egg) before it divides and develops (see http://learn.genetics.utah.edu/features/pharming/).

Technology such as this has already assisted humans in developing many life-saving protein drugs such as insulin, which is used to treat diabetes. Gene technology allows human proteins that are provided only by mammals, to be manufactured, thus treating diseases and saving lives (Gillespie, 2007). Farm animals such as cattle are advantageous for this practice as they have high reproductive capacity and are easy to care for and maintain (Gillespie, 2007). The proteins produced are present in blood and milk produced by the animals, which can then be easily collected for further research and drug development.

Despite the potential life-saving advantages of gene farming animals for protein and drug development, the moral and ethical dilemma’s associated with the issue are of great concern. Gene farming for pharmaceuticals has the potential to cause significant harm to the animals involved, by infecting the animal with viruses, as well as interrupting the animal’s normal gene functionality that can result in abnormalities (Straughan, 2004).

HOG a kidney - future reality?


Approximately, 180 000 people around the globe are currently waitlisted for an organ transplant and fewer than one out of three people will survive. Could pigs be the solution to this devastating medical predicament??
Xenotransplantation, is the transplantating of living cells, tissues or organs from one animal species to another. Currently, xenotransplants is mainly focused on transplanting organs in particular from pigs to human due to physiological similarities. Genetically engineered pigs with the hyperacute rejection gene knocked out are used as organ, tissue and cell donors for a myriad of diseases and illness in humans.
To turn this possible medical breakthrough into a reality, however, a number of obstacles must be dealt with including zoonosis, further genetic engineering to prevent rejection due to the enzyme a-1,3 galactosyltransferase present on pig cells and a range of ethical and religious dilemmas.
One of the obstacles, xenozoonosis, is mainly concerned with creating a public health disaster such as epidemics or pandemics and the transmission of porcine endogenous retroviruses and swine influenza from pigs to humans. Where genetics plays a key role is in the inactivation of the enzyme a-1,3 galactosyltransferase present on pig cells which creates a sugar that the human body recognizes as foreign and leads to immune rejection. Religious dilemmas could be raised because it is against some relegions to eat pork. Animal welfare and ethics have been put foward as major issues in xenotransplantation. Is it humane and ethical to raise pigs solely for human benefits? Unless these issues are resolved xenotransplants will remain only a “possible” medical breakthrough.



by: Sonia Vaswani (41310832)
Primary references:
Cozzi, E and Ancona, E , 2003, 'Xenotransplantation, where do we stand?' Journal of nephrology , vol. 16, no. 7, pp.16-21
Access article here

Dobson, R.A., 2002, ‘Scientists produce genetically engineered, cloned pigs for xenotransplantation.’ BMJ, vol. 324, no. 673
Access article here

Secondary references:
Cox, A. and Zhong, R., 2005, ‘Current advances in xenotransplantation’ Hepatobiliary pancreatic disease Int, vol. 4, no. 4, pp. 490-494
Acces article here

They’re larger than life and will light up your life: Transgenic Fish


A transgenic organism is genetically engineered to express genes from another species by inserting the desired gene into the DNA of a fertilized egg. Many species of fish have had a transgene inserted into their genome to produce a desired phenotypic characteristic. The most common phenotype targeted is growth rate. This is achieved by incorporating a growth hormone gene into the DNA of the fish. At the other end of the spectrum, researchers at the National University of Singapore incorporated the fluorescence gene from a sea anemone into a zebra fish. The result was a fish that fluoresced. Commonly called the Glofish, it became the first marketed transgenic pet.

The production of transgenic fish for commercial trade would provide many advantages to fishing industries worldwide; however faces many ethical limitations.

Transgenic Salmon with an incorporated growth hormone gene grow to extraordinarily large sizes within the same time span as compared with their wild type counterparts. This would increase the rate of aquaculture production by lowering the age at which target sale weight is reached, thus providing positive effects for the fishery industry. Also, the novelty of owning a fluorescing fish has developed and promoted a highly profitable commercial market for the Glofish within the pet industry.
A major limitation to any genetic modification is ethical considerations. Concerns about possible food safety issues and environmental impact of transgenic fish have restricted commercialisation and global trade. California, Canada, and the European Union have prohibited the import and sale of genetically modified fish for these reasons.
Miranda Flinn (41186194)

Identifying bacterial species by making cloned DNA probes

Many bacterial species that are part of the Campylobacter group have been identified as disease – causing agents of animals and humans. One species that is of veterinary importance is Campylobacter hyointestinalis, which causes proliferative enteritis in pigs and other animals. However, many Campylobacter species appear similar, making it difficult to confidently diagnose which species is infecting a patient using visual identification methods. This delays proper treatment and causes confusion as to which species is causing disease if there are multiple species present.

Instead of using visual differences between species to determine which Campylobacter species is causing disease in a patient, probes for particular species are being developed by cloning DNA fragments from the bacteria’s chromosomes. These DNA probes will allow for rapid identification of different Campylobacter species because a DNA probe will only form a hybrid with the DNA of the species it was cloned from and not any other species, even if they are similar.

Campylobacter hyointestinalis probes were made by cloning fragments of chromosomal DNA into a plasmid vector, and allowing the fragments to be combined into the plasmid DNA as it replicated. The probes were then mixed with Campylobacter hyointestinalis and Campylobacter fetus, to see which probes would show specificity for Campylobacter hyointestinalis. When these probes were tested in samples from animal specimens, they only formed hybrids with Campylobacter hyointestinalis. This demonstrates cloned DNA probes are a quick, efficient method of identifying specific disease – causing bacteria in an animal, leading to faster diagnosis and treatment of diseases.

If you wish to read about other experiments within veterinary medicine that involve cloning DNA, follow these links:

http://cvi.asm.org/cgi/reprint/12/2/334

http://journals.cambridge.org/download.php?file=%2FPAR%2FPAR125_03%2FS0031182002002019a.pdf&code=62919565bfd61c5f0e7fa9d615b280fd