The Production Of Pharmaceuticals Using Transgenic Animals Is Called .

Pharmaceutical production using transgenic animals, also known as pharmaceutical farming or biopharming, represents a groundbreaking approach to producing complex therapeutic proteins and pharmaceuticals. This innovative field harnesses the power of genetic engineering to modify animals, enabling them to produce valuable substances in their milk, blood, eggs, or other tissues. This article explores the intricacies of this technology, its potential benefits, challenges, and future directions.

Introduction to Pharmaceutical Farming

Pharmaceutical farming revolves around the creation of transgenic animals, which are animals whose genetic material has been altered to include a specific gene or genes from another species. This foreign gene, called a transgene, instructs the animal's cells to produce a desired protein or pharmaceutical compound.

The fundamental concept is elegantly simple: transform animals into living bioreactors. Instead of relying on traditional methods like cell cultures or chemical synthesis, biopharming offers a potentially more efficient and cost-effective way to generate large quantities of complex proteins. These proteins can then be extracted, purified, and formulated into pharmaceutical products.

How are Transgenic Animals Created?

The creation of transgenic animals for pharmaceutical production is a multi-step process requiring precision and specialized techniques. Here's a breakdown of the common methods used:

1. Microinjection

• Process: This method involves directly injecting the desired transgene into the pronucleus of a fertilized egg. The pronucleus is the nucleus of the egg or sperm cell before they fuse to form the zygote nucleus.
• Procedure:
  • Fertilized eggs are collected from donor animals.
  • Using a fine needle, the transgene DNA is injected into the pronucleus.
  • The injected eggs are implanted into surrogate mothers.
  • Offspring are screened to identify those that have successfully integrated the transgene into their genome.
• Advantages: Relatively simple and widely applicable to various animal species.
• Disadvantages: Low efficiency, as the transgene integration is random and unpredictable. The transgene may not be expressed at high levels or in the desired tissue.

2. Retroviral Vectors

• Process: Retroviruses are viruses that can integrate their genetic material into the host cell's DNA. In this method, the transgene is inserted into a modified retrovirus, which then infects early-stage embryos.
• Procedure:
  • A retroviral vector is engineered to carry the desired transgene.
  • Embryos are infected with the retroviral vector.
  • The virus integrates the transgene into the embryo's genome.
  • The embryos are implanted into surrogate mothers.
  • Offspring are screened for transgene integration and expression.
• Advantages: Higher efficiency of transgene integration compared to microinjection.
• Disadvantages: Potential for insertional mutagenesis (the transgene disrupting endogenous genes) and limited size of the transgene that can be delivered.

3. Somatic Cell Nuclear Transfer (SCNT) - Cloning

• Process: SCNT, also known as cloning, involves transferring the nucleus of a somatic cell (any cell other than a sperm or egg cell) into an enucleated egg cell (an egg cell that has had its own nucleus removed). If the somatic cell has been genetically modified to contain the transgene, the resulting animal will also carry the transgene.
• Procedure:
  • Somatic cells are genetically modified to include the desired transgene.
  • The nucleus of a somatic cell is transferred into an enucleated egg cell.
  • The reconstructed egg is stimulated to divide and develop into an embryo.
  • The embryo is implanted into a surrogate mother.
  • Offspring are screened for transgene integration and expression.
• Advantages: High efficiency of transgene integration and allows for precise gene targeting.
• Disadvantages: Technically challenging and can be expensive. Raises ethical concerns related to animal cloning.

4. CRISPR-Cas9 Gene Editing

• Process: CRISPR-Cas9 is a revolutionary gene-editing technology that allows for precise targeting and modification of DNA sequences. It can be used to insert, delete, or replace genes in the animal's genome.
• Procedure:
  • A guide RNA (gRNA) is designed to target a specific DNA sequence in the animal's genome.
  • The gRNA and Cas9 enzyme (an enzyme that cuts DNA) are introduced into cells.
  • The gRNA guides the Cas9 enzyme to the target DNA sequence, where it makes a cut.
  • The transgene can then be inserted at the cut site through a process called homology-directed repair.
  • Modified cells are used to create transgenic animals through SCNT or other methods.
• Advantages: Highly precise, efficient, and versatile. Allows for targeted gene insertion and modification.
• Disadvantages: Potential for off-target effects (the Cas9 enzyme cutting at unintended sites in the genome) and ethical concerns related to gene editing.

Which Animals are Used in Pharmaceutical Farming?

Various animal species can be used for pharmaceutical farming, each with its advantages and disadvantages. The choice of animal depends on several factors, including the complexity of the protein to be produced, the desired production volume, and regulatory considerations. Here are some of the most commonly used animals:

1. Goats

• Advantages: Relatively short gestation period, high milk production, and well-established transgenic technology. Goats are particularly well-suited for producing proteins in their milk.
• Examples: Atryn, an anticoagulant drug produced in goat milk, was the first human pharmaceutical approved for production in transgenic animals.

2. Cows

• Advantages: Very high milk production, which allows for large-scale production of therapeutic proteins.
• Disadvantages: Long gestation period and higher maintenance costs compared to smaller animals.
• Examples: Research is ongoing to produce antibodies and other therapeutic proteins in cow milk.

3. Sheep

• Advantages: Similar to goats, with a relatively short gestation period and good milk production.
• Disadvantages: Lower milk production compared to cows.

4. Rabbits

• Advantages: Short gestation period and relatively easy to handle. Rabbits can be used to produce proteins in their milk or blood.
• Disadvantages: Lower production volume compared to larger animals.

5. Chickens

• Advantages: Lay eggs frequently, which can be a convenient way to harvest therapeutic proteins. The proteins are produced in the egg white.
• Disadvantages: Glycosylation patterns in chicken eggs may differ from those in humans, which could affect the efficacy of some therapeutic proteins.
• Examples: Research is underway to produce antibodies and other therapeutic proteins in chicken eggs.

6. Pigs

• Advantages: Organs and tissues are physiologically similar to humans, making them a potential source for xenotransplantation (transplantation of organs or tissues from one species to another).
• Disadvantages: Longer gestation period and higher maintenance costs compared to smaller animals. Ethical concerns related to using pigs for pharmaceutical production and xenotransplantation.

What Types of Pharmaceuticals Can Be Produced?

Transgenic animals can be engineered to produce a wide range of pharmaceutical products, including:

• Monoclonal Antibodies: These are highly specific antibodies that can target and neutralize disease-causing agents or cancer cells.
• Blood Clotting Factors: Such as Factor VIII and Factor IX, which are used to treat hemophilia.
• Enzymes: Used to treat enzyme deficiencies or as therapeutic agents in various diseases.
• Hormones: Such as insulin and growth hormone, used to treat diabetes and growth disorders.
• Vaccines: Transgenic animals can be used to produce vaccine antigens, which can then be used to develop vaccines against infectious diseases.
• Cytokines: Proteins that regulate the immune system and can be used to treat autoimmune diseases and cancer.

Advantages of Pharmaceutical Farming

Pharmaceutical farming offers several potential advantages over traditional methods of pharmaceutical production:

• Cost-Effectiveness: Biopharming can be more cost-effective than traditional methods, especially for complex proteins that are difficult to produce in cell cultures or through chemical synthesis.
• Scalability: Animal herds can be expanded to increase production volume, allowing for rapid scale-up to meet market demand.
• Complex Protein Production: Transgenic animals can produce complex proteins with proper folding and post-translational modifications, which are essential for their biological activity. These modifications can be difficult to achieve in other production systems.
• Reduced Capital Investment: Compared to building and maintaining large-scale cell culture facilities, pharmaceutical farming can require less upfront capital investment.

Challenges and Concerns

Despite its potential benefits, pharmaceutical farming also faces several challenges and concerns:

• Regulatory Hurdles: The regulatory landscape for biopharming is complex and varies across countries. Companies must navigate stringent regulations related to animal welfare, environmental safety, and product quality.
• Public Perception: Some people have concerns about the ethical implications of genetically modifying animals and using them for pharmaceutical production.
• Contamination Risks: There is a risk of contamination of pharmaceutical products with animal pathogens or other unwanted substances. Strict quality control measures are needed to minimize this risk.
• Glycosylation Differences: Glycosylation is the process of adding sugar molecules to proteins. The glycosylation patterns in animals may differ from those in humans, which could affect the efficacy or immunogenicity of therapeutic proteins.
• Transgene Stability: The transgene may not be stably integrated into the animal's genome, leading to reduced protein production over time.
• Animal Welfare: Ensuring the welfare of transgenic animals is a paramount concern. Animals must be housed and cared for in a humane manner.

Ethical Considerations

The use of transgenic animals for pharmaceutical production raises several ethical considerations:

• Animal Welfare: The genetic modification and use of animals for pharmaceutical production can raise concerns about animal suffering and well-being. It is essential to ensure that animals are treated humanely and that their welfare is prioritized.
• Environmental Impact: The potential environmental impact of biopharming, such as the escape of transgenic animals into the wild or the spread of transgenes to other organisms, needs to be carefully considered.
• Public Acceptance: Public acceptance of biopharming is crucial for its success. Open and transparent communication about the benefits and risks of the technology is essential to address public concerns.
• Intellectual Property: The development and commercialization of biopharmaceuticals raise complex intellectual property issues, such as patent rights and access to medicines.

The Future of Pharmaceutical Farming

The field of pharmaceutical farming is rapidly evolving, with ongoing research and development efforts focused on improving the efficiency, safety, and ethical acceptability of the technology. Some of the key areas of focus include:

• Improving Transgene Expression: Researchers are working on developing new strategies to increase the expression levels of transgenes in animals. This includes optimizing the design of transgenes, using stronger promoters, and targeting transgene integration to specific locations in the genome.
• Humanizing Glycosylation Patterns: Efforts are underway to engineer animals with human-like glycosylation pathways, which would improve the efficacy and reduce the immunogenicity of therapeutic proteins.
• Developing New Animal Models: Researchers are exploring the use of new animal models, such as genetically engineered cell lines and insects, for pharmaceutical production.
• Enhancing Animal Welfare: Continued efforts are needed to improve the welfare of transgenic animals, including developing more humane housing and handling practices.
• Strengthening Regulatory Frameworks: Clear and consistent regulatory frameworks are needed to ensure the safety and quality of biopharmaceuticals and to address ethical concerns.

Case Studies

Several biopharmaceutical products produced in transgenic animals have already been approved for human use, demonstrating the potential of this technology. Here are a few notable examples:

• Atryn (Antithrombin): Produced in the milk of transgenic goats, Atryn is an anticoagulant used to prevent blood clots in patients with hereditary antithrombin deficiency. It was the first human pharmaceutical approved for production in transgenic animals by the FDA.
• Ruconest (C1 Esterase Inhibitor): Produced in the milk of transgenic rabbits, Ruconest is used to treat acute angioedema attacks in patients with hereditary angioedema.

These examples highlight the potential of pharmaceutical farming to produce valuable therapeutic proteins that can improve human health.

Conclusion

Pharmaceutical production using transgenic animals holds immense promise for revolutionizing the way we produce complex pharmaceuticals. By harnessing the natural biological machinery of animals, biopharming offers a potentially more efficient, cost-effective, and scalable alternative to traditional production methods. While challenges and ethical considerations remain, ongoing research and development efforts are paving the way for a future where transgenic animals play an increasingly important role in the production of life-saving medicines.

The future of biopharming hinges on addressing the existing challenges, promoting ethical practices, and fostering public trust. As technology advances and regulatory frameworks evolve, transgenic animals are poised to become an integral part of the pharmaceutical landscape, offering new hope for treating a wide range of diseases.