How We Can Combat Bird Flu by Applying Gene Editing

By Jodie Lechtenberg

Jodie Lechtenberg
Insights of Nature
8 min readOct 15, 2023

--

Imagine a world where our favorite chicken nuggets are not just delicious but also safe from the threat of bird flu. Well, there's a gene-editing tool called CRISPR-Cas9 that could make this dream a reality. It's not just about your nuggets, it's about all of our nuggets!

Each year a staggering 74 billion chickens are consumed globally. So this isn't just a you problem, it's an everyone problem.

To put it in perspective, bird flu is spreading ceaselessly, causing the deaths of over 100 million chickens and several hundred human lives…

every

single

year.

It's a serious issue that we cannot ignore any longer.

In this article, we'll dive into CRISPR-Cas9 technology that could help us combat the bird flu, protect our feather friends, our own health, and make those nuggets safer to enjoy!!

Understanding the bird flu

Bird flu is a contagious viral infection that primarily affects birds. It can be caused by several different strains of influenza viruses, with the most common ones being H5N1 and H7N9.

Viral Strains: Bird flu is caused by influenza A viruses. These viruses are classified based on the surface proteins hemagglutinin (H) and neuraminidase (N). For example, H5N1 shows the specific combination of these proteins. Some strains are highly infectious, causing severe illness in birds and sometimes even humans.

Transmission: The virus spreads among birds through direct contact with infected ones, their saliva, feces, and sneezes. Migratory birds can also carry the virus and spread it to new areas. Humans can get infected through contact with infected birds, their dirty environments, or by consuming undercooked poultry products.

Symptoms in Birds: In birds, bird flu can cause a wide range of symptoms, including
breathing difficulties, swollen heads, and a drop in egg production. Highly infectious strains can be terrible for bird populations.

Pandemic Concern: There is concern about the potential for bird flu viruses to mutate or reassort with human influenza viruses, leading to a strain that is both highly contagious and easily transmissible among humans. Such a development could lead to a global pandemic.

CRISPR-Cas9

What is CRISPR-Cas9?
CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) and Cas9 (CRISPR-associated protein 9) are part of a revolutionary gene-editing system. CRISPR is like a genetic "memory" system, and Cas9 is the "molecular scissors" that allow precise editing of genes.

How does it work?

Targeting Specific Genes: The key to CRISPR-Cas9's power is its ability to precisely target and modify specific genes in an organism's DNA.

RNA: To target a specific gene, scientists design a piece of RNA (similar to DNA but a single-stranded version) that matches the gene's sequence. This RNA is like a "search query." It's designed to find and attach to the gene's sequence of nucleotides.

Cas9 Molecular Scissors: Think of Cas9 as a pair of scissors that can cut DNA. These scissors are guided by the RNA to the exact spot in the DNA where the targeted gene is located.

Cell's Repair Process: The cell has a built-in repair mechanism. When the Cas9 cut is made at that specific location, the cell recognizes that there's a break in the DNA and then tries to fix it. This is where scientists can influence the outcome. By providing a new piece of genetic material, they can effectively modify the genetic code or disable it.

Potential to combat bird flu

Scientists can use CRISPR to modify the DNA of chickens, making them more resistant to avian influenza. For example, they can edit genes related to the chicken's immune system to boost its ability to fight off the virus. Another approach is to target the proteins that the virus uses to enter the chicken cells.
The bird flu often spreads from wild birds to domestic poultry. CRISPR could be used to modify wild bird populations by making them less vulnerable to the virus. This would help reduce the chance of transmission to domestic birds. It can also be used to modify the avian influenza virus itself. By changing specific genes in the virus, researchers can weaken the ability to cause disease in chickens while preserving its immunogenicity.

How can we use CRISPR-Cas9 to make chickens resistant to bird flu?

CRISPR-Cas9 involves the precise targeting and editing of specific genes, like HA and NA, in the bird flu virus's genome. This process includes the use of various proteins and components, such as Cas9, gRNA, and cellular repair machinery, to modify or eliminate harmful genes:

Genetic Analysis and Target Selection: Scientists begin by sequencing the entire genome of the bird flu virus, identifying specific genes such as:
- HA Gene (Hemagglutinin): This gene encodes the hemagglutinin protein, a critical component for viral entry into host cells.
- NA Gene (Neuraminidase): This gene encodes the neuraminidase protein, which is important for the release of new viral particles from infected cells.

CRISPR System Components:
The CRISPR system includes the Cas9 nuclease (it’s an enzyme that makes precise double-stranded cuts in the viral DNA. The Cas9 protein uses specific domains like;
- RuvC domain: Responsible for cleaving one DNA strand.
- HNH domain: Involved in cleaving the complementary DNA strand), and the guide RNA (gRNA), which is custom-designed and consists of two key components:
- CRISPR RNA (crRNA): This part of the gRNA is responsible for recognizing and binding to the target DNA sequence in the bird flu virus.
- TracrRNA: TracrRNA serves as a frame, helping to stabilize and guide the Cas9 protein.

The delivery system is called viral vectors and these are commonly used for efficient CRISPR-Cas9 delivery. These vectors are engineered to transport the CRISPR components, such as Cas9 and gRNA, into the infected chicken cells.
The gRNA (CRISPR RNA and tracrRNA) binds specifically to the target gene in the bird flu virus.

The host cell's repair mechanisms are intrinsic and involve various proteins, including:
- Ku Protein: Recognizes DNA breaks and initiates the repair process.
- DNA Ligase: Enzyme responsible for sealing the DNA strands after repair.

After editing, scientists validate the changes in the viral DNA by DNA sequencing to confirm that the harmful gene, such as HA or NA, has been either eliminated or modified.

Safety and efficacy Testing: Many safety assessments follow, including various stages of testing. This may involve monitoring the edited virus in cell cultures, animal models, and, if necessary, clinical trials.
- PCR (Polymerase Chain Reaction): A technique for amplifying and detecting DNA sequences.
- Sequencing Technologies: Used to confirm precise genetic changes and evaluate the edited virus.

Did it work?

To see if the genetic changes in the chickens really worked, scientists infected them with bird flu. Here's what they found:

Low Virus Dose: When they used a small amount of the virus, nine out of ten genetically modified chickens stayed healthy. This was a good sign, showing that the genetic changes protected most of the chickens from the virus.

What makes this even more fascinating is that the virus didn't give up. When faced with the stronger virus dose, it started mutating its own genes. These changes allowed the virus to become a bit different, and in some cases, it still managed to make the modified chickens sick.

Challenges

In an effort to achieve full resistance against the bird flu virus, scientists attempted to eliminate an essential protein called ANP32A from the chickens' DNA. They believed that by doing so, the chickens would become completely immune to bird flu. Here's what they found:

Targeting ANP32A: ANP32A is a protein in the chicken's cells that the bird flu virus relies on to replicate and spread. The scientists aimed to remove or deactivate the gene responsible for making ANP32A, thinking that without this protein, the virus wouldn't be able to infect the chickens.

Unexpected Outcome: However, what they discovered was unexpected. Even without ANP32A, the virus found a way to sneak into the chicken cells. It turned out that the virus could exploit similar proteins called ANP32B and ANP32E, which were still present in the chicken's cells.

Potential solutions to these challenges

To tackle the bird flu virus's adaptability by using proteins like ANP32A, ANP32B, and ANP32E, scientists could consider the following;

Combination Genetic Modifications: Instead of focusing on just one protein, scientists might target ANP32A, ANP32B, and ANP32E. By disrupting all these proteins, they create multiple barriers, making it much more difficult for the virus to find a way in.

Antiviral Medications: Researchers could develop drugs that specifically inhibit the functions of these proteins. For instance, drugs targeting ANP32A, ANP32B, and ANP32E could hinder the virus's ability to infect and replicate in host cells.

Ethical considerations

Animal Welfare: Genetic modifications can impact the well-being of the chickens.
Ecosystem Impact: There is a potential risk of modifying the natural behavior or characteristics of birds.
Unintended Consequences: Genetic modifications can have unforeseen effects.
Regulatory Oversight: Creating robust regulatory frameworks for gene-edited animals is essential.
Informed Consent: If gene-edited animals are released into the environment, obtaining informed consent from communities and individuals who might be impacted, is important
Equity and Access: Ensuring that the benefits of gene-edited chickens reach all parts of society, including small-scale farmers, etc.
Long-term Monitoring: There should be continuous monitoring of the gene-edited chickens to assess their impact on both the environment and animal welfare over time.

_________________________________________________________________

In a world where bird flu is a serious threat to both chickens and humans, CRISPR-Cas9 emerges as a super cool tool that might change the outcome. It's not just about making chicken nuggets tastier; it's about making sure we can enjoy them safely without worrying about bird flu.

It’s an enormously big deal. Every year, it kills over 100 million chickens and even harms hundreds of people.

CRISPR-Cas9 is like a superhero for chickens. With this tech, scientists can modify the genes of chickens to make them resistant to bird flu.

But, there are some tough parts too. The virus can be sneaky, and it can still find ways to infect the chickens, even after we use CRISPR.

As we move forward with CRISPR, we have to remember to be kind to animals and be careful. We also need rules to use this cool technology wisely and responsibly.

By thinking about the animals, protecting the environment, and being careful with our superpowers, we can make the world a safer place for both chickens and us.

“In this adventure, it's not just about making better chicken nuggets; it's about creating a healthier world for everyone” 🌎🌿☀️

the world is in our hands.

--

--

Jodie Lechtenberg
Insights of Nature

intellectually curious individual, excited to learn about everything