There are about 2% of children worldwide who are allergic to eggs and this condition make them unable to receive a number of routine vaccinations because those vaccines are produced using chicken eggs. This happened to an 11-year-old-girl whose father, Timothy Doran is a molecular biologist at the Commonwealth Scientific and Industrial Research Organization (CSIRO) in Australia.

A powerful gene editing tool CRISPR came into Doran’s mind in his attempt to produce eggs safe for everyone. Most egg allergies are caused by one of just four proteins in the white. When the gene that encodes for one of these proteins was altered, the protein produced could no longer trigger a reaction in blood serum from people who were known to be allergic to it. Scientists are working on producing not only the hypoallergenic eggs but also the chickens that lay those eggs, using the cutting-edge technology – gene editing.

Chicken as an Animal Model

Being the closest living relative to the Tyrannosaurus rex dinosaur, chickens are often used in avian physiological study because they are easy to keep, and have been bred domestically for many years, so a great amount of information on their physiology is available.

The chicken has been emphasized as an animal model due to its unique development and reproduction system. Since chickens are vertebrates, their developmental process has many characteristics in common with humans, despite there are many differences. Chickens have provided valuable information of the development of nervous system, showing how cells migrate and differentiate.

Moreover, the molecular basis of limb development is also discovered through chickens as the process is similar in humans and birds. All these helped human in the understanding of numerous limb disorders.

Apart from that, scientists study the genetic pathways that regulate early patterning events and lineage commitment using the chicken embryo as it is an established model perfect for the study. Chickens also play a pivotal role as a comparative model for the study of mammalian embryogenesis.

A great example is the study of the chick embryo development that reveals clues about the atrial septal defect of human’s heart. This heart condition is often referred to as ‘hole in the heart’. It is a condition in which the wall between the left and right atria of the heart does not close completely during development, making it difficult for the heart to pump blood around the body.

Chick embryos are being used to model this condition, because they have a four-chambered heart just like humans. Scientists are currently investigating the involvement of a particular gene that leads to this condition by incorporating it into the chick’s cells. This study in chickens will help to understand the role of this gene in the development of the heart.

The studies above are all carried out presently, in fact, the usage of chickens in research can be dated back to as early as 1911 where chicken provided some ideas to one of the earliest models of cancer growth and spread, which led to the discovery of the Rous sarcoma virus by Peyton Rous. The identification of the Rous sarcoma virus enabled the studies of how viruses cause tumors and the treatments of hormone to suppress the cancer growth in rats, mice, rabbits, chickens, primates, and horses. In 1966, Rous received the Nobel Prize for his discovery.

Consumption of Chickens and Eggs

The chicken is a key agricultural commodity accounting for 30% of the worldwide meat production. The Food and Agriculture Organization (FAO) forecasts poultry meat consumption to reach almost 133 million tons by 2024, compared to 111 million tons in 2015. Chickens will be the world’s most eaten meat by weight by 2020, overtaking pork. As a broad rule, chicken meat accounts for around 89 per cent of poultry meat availability, so by 2024 the consumption of chicken could well be around 118 million tons. The rising consumption of chicken is mainly because people nowadays consider chicken as a healthier meat for their diet.

Currently, China, the U.S., Indonesia, and Brazil are the world’s biggest chicken producers.

On the other hand, it was reported that global egg production reached 69.8 metric tons in 2014 while the consumption per-person was 210 eggs. These numbers will be increasing every year as the awareness of people on nutrients provided by eggs keeps increasing.

Similar to the list of world’s largest chicken producers, China, again tops the list of largest egg producing countries in the world with a 40% share in the global egg production. The country has experienced tremendous growth in the poultry sector over the last twenty years. Egg production has increased vigorously from merely 5.35 million tons in 1995 to 29 million tons in 2013, by almost 6-folds.

Owing to all the reasons above, it is essential to precisely and genetically edit the chicken genome which not only allow the investigation of key developmental signaling pathways in avian species but also examine genes involved in egg and meat production, disease resistance, and to promote the sustainability and biosecurity in both livestock and poultry production.

Applications of Gene Editing in Chicken

Over 50 billion chickens are eaten globally each year and soon poultry meat will become the most popular meat consumed in the world. With the increase in world population and the worsening impacts of climate change, humans need to consider using all the tools available to improve the genetics of chickens and other poultry animals in order to prevent the lack of food supply.

Improving productivity in poultry is carried out through traditional genetics but managing the threat of infectious diseases is still a major problem. This can be overcome by using an emerging technology which is able to precisely edit the genome in chickens to confer resistance to major diseases such as the bird flu.

In fact, a number of projects are already in development using genome editing to confer resistance to major diseases in poultry and crops, for instances, the porcine respiratory disease in pigs and powdery mildew in wheat.

However, the genetic manipulation of chickens has lagged far behind compared to other organisms because of the difficulty in accessing and manipulating the zygote. Therefore, chicken transgenesis has mainly been performed using viral vector infection of the early stage embryo.

A significant difference of chicken from other vertebrate species is that its primordial germ cells (PGCs) can be propagated in vitro via suspension and the germ line competence can also be maintained even after transplanting back into donor embryos.

Adult Female Sterility

A group of researchers from the University of Edinburgh used a powerful gene editing tool called Transcription activator-like effector nucleases (TALEN) to delete part of a chicken gene, DDX4 that is related to fertility. The resulting chickens which lack DDX4 were sterile – not producing eggs but were healthy in all other ways.  

They found that the DDX4 is needed for proper oocyte differentiation. The primordial germ cells – the specialized cells that lead to the formation of egg, were initially formed in chickens with DDX4 knockout but were lost during meiosis in the developing ovary ultimately causing adult female sterility.

You would probably ask, “What can we do with sterility in hens?”

Researchers could implant these primordial germ cells into eggs that would eventually hatch into the genetically edited surrogate hens. These surrogate hens would then produce eggs that are genetically whatever breed they had been implanted with.

This is an important step in saving and protecting rare poultry breeds from loss in order to preserve future biodiversity of poultry especially under various climate stresses.

Enhancement of Targeted Editing in Chicken Cells

The robust gene editing tool CRISPR has enabled highly efficient genome targeted editing for various organisms but studies focused on CRISPR-mediated chicken genome editing are rarely seen compared with mammalian genomes.

In a recent study, a team of researchers have combined CRISPR with yeast Rad52 (yRad52) to enhance targeted genomic DNA editing in chicken DF-1 cells. The efficiency of targeted mutations in the chicken genome was increased to 41.9% when the CRISPR and yRad52 were used together.

This study proves that CRISPR combined with yRad52 significantly enhances gene editing in chicken and this approach could be extensively applied in other organisms.

Egg Protein Modification

The market value of biopharmaceutical has been increasing due to the advances in biotechnology. In order to cope with the rising demand of pharmaceutical proteins as world population grows, the chicken has been selected as a great candidate of being a bioreactor for economical mass production of human therapeutic proteins because chicken lays more than 300 eggs per year. Thus, pharmaceutical proteins could be yielded economically.

Eggs are an important source of protein, but some of the proteins in eggs including ovomucoid, ovalbumin, ovotransferrin and lysozyme can pose life concerns in young children. Ovomucoid is known to be the most allergenic and predominant allergen and it is found in the chicken egg white.

People who suffer from egg allergy can go into potentially fatal anaphylactic shock that could lead to death if they consume eggs. There is currently no long-term cure for egg allergy. Strict avoidance of egg is the best way to prevent one suffering from egg allergy. However, avoiding eggs completely is impossible because they might be traces of egg present in various food products, pharmaceutical products, and vaccines.

The experts in Deakin University and CSIRO Australia are attempting to use CRISPR to edit the gene in chickens that could result in hypoallergenic eggs. They have been working on extracting those four proteins that cause allergy, silence the allergenic parts of them, then reintroducing the non-allergenic proteins back into the egg. The chicken subsequently born from that egg should in turn lay hypoallergenic eggs.

Gene editing could contribute to produce the customized eggs avoiding harmful effects.

The Pink Chicken Project

An expert group announced last year that a new geological epoch, the Anthropocene, should be declared to prove humanity’s impacts on the Earth. In order to define a geological age, it is essential to find global physical evidence of the transition that will be preserved for future geologists.

The prime candidate for this is none other than the chicken.

Perhaps, you would be asking why the chicken was selected.

The chicken was first domesticated almost 8,000 years ago from the red jungle fowl, Gallus gallus, which was native to south-east Asia. The chicken was carried all over the world over subsequent millennia, and eventually become the world’s most common bird. It has been fossilized in thousands of landfill sites and on street corners around the world. Hence, to the Anthropocene geologists, it is a great physical evidence of the transition.

To mark the beginning of the Anthropocene, a group of scientists has started the Pink Chicken Project which suggests changing the color of the entire species Gallus Gallus Domesticus to pink. The pink color would come from a gene from the insect cochineal. The modification would be carried out using the gene editing technique CRISPR, with adoption of the pink color accelerated by a gene drive, a mechanism for increasing the odds an offspring will inherit a trait, in this case the color pink from its parents.

The species could then be permanently altered, on a global scale, in just a few years. By that time, no white chicken would have left and bright pink bones would peek out every time you bite into a chicken wing.

The Pink Chicken Project is meant to leave reminders for future generation of humanity’s impact on the environment in the form of discarded pink chicken bones.

What future geologists will find in the Earth crust of the 20th century? It would be nuclear waste, plastic, and fossilized pink chicken bones (not forgetting the CRISPR technology) if the Pink Chicken Project is successful.

Expectations of Gene Editing in Chickens

Studies of gene editing in chicken should be carried out more extensively since the approaches to enhance efficiency of gene editing in chickens are gradually increasing. There are many areas that researchers could look into when come to gene editing in chickens. Disease resistance is among the areas to study especially the avian influenza (AI) on chickens.

The prevention of avian viral disease that potentially threatening human society and poultry production has been performed by gene editing technology. Transgenic chickens expressing short-hairpin RNA (shRNA) targeting AI virus gene related with viral transmission was produced in the study and showed decreased viral transmission ability. This finding contributes greatly to human society as the disease could pose potential threats to human.

Egg protein modification is another area worth studying as some vaccines are produced using eggs. The proteins in eggs have to be altered to become less allergenic or completely not allergenic for safe use. In addition, people who are allergic to eggs could have the opportunity to taste eggs in their lives. Who doesn’t want a birthday cake on their birthday? If hypoallergenic eggs are successfully produced, it would be the greatest news for those who suffer from egg-allergy.

Rapid development of biotechnology and in vitro culture system of germline competent cells have increased the value of chickens not only for industrial areas but also research fields. Therefore, highly efficient and precise gene editing tools are urgently in need to improve poultry in several areas especially meat and egg quantity and quality, enhance disease resistance ability, and to produce protein drugs. To date, TALEN and CRISPR systems are proven to be efficient tools when it comes to gene editing in chickens.  

Image from flickr by Lindsay Holmwood

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