Medical Biotechnology II - Lewis

What is Therapeutic Biotechnology?

Therapeutic biotechnology uses biological systems, organisms, or processes to diagnose, prevent, or cure disease.
• Core tools are recombinant DNA, cell culture, and gene delivery vehicles.
• Its outputs include recombinant proteins, antibodies, vaccines, viral vectors, and cells.
• The field is inspired by biological insights, but defined manufacturing capabilities.

What are the three therapeutic logics?

Preventions, Supplementation, and Replacement

What is prevention?

reduce the chance that disease starts or progresses.
Prophylactic vaccines and risk-reducing immune interventions.
E.g., vaccines against infectious disease, cancer, etc

What is supplementation?

add a missing or insufficient activity without fully rebuilding the system.
E.g., insulin, erythropoietin, factor VIII, cytokines, enzyme replacement,
cancer monoclonal antibodies

What is replacement?

restore a missing gene, cell population, tissue, or organ-
level function.
E.g., gene therapy, regenerative medicine and tissue engineering,
hematopoietic stem-cell transplantation, skin grafts.

What is a therapeutic target?

defined by disease biology

What is a modality choice?

small molecule, protein, nucleic acid, or cell; to be determined by clinical needs and biology.
• Where will it be delivered?
• How long is the therapy needed?
• What is the most effective intervention?

What is a bioprocess design?

how will you make the
therapeutic? Impacts if the product can be made
reproducibly (quality) and at scale (quantity)

Clinical translation depends on…

potency, safety, delivery, quality control, and cost

What are the major therapeutic modality classes?

• Small molecules: from fermentation, biocatalysis, and metabolic engineering.
• Nucleic-acid medicines: Anti-sense oligonucleotides, mRNA, etc.
• Recombinant proteins: enzymes, monoclonal antibodies, etc.
• Vaccines: can be peptides, protein, RNA, carbohydrates, etc.
• Gene therapies: viral delivery of DNA repairs
• Cell therapies: engineered cells
• Regenerative medicine products: engineered tissue

How biotechnology makes small-molecule drugs?

• Fermentation - growing a production strain under tightly
controlled conditions.
• Metabolic engineering - redirect carbon flux toward the
desired pathway.
• Process engineering - optimizes feeding, oxygen, pH, and
extraction.
• Downstream purification - determines product quality
and economics.

What are therapeutic nucleic acids?

• Short, synthetic nucleic acid drugs designed to modulate gene expression or RNA function
• Antisense oligonucleotides (ASOs), siRNA, mRNA therapeutics, and some aptamers
• Targeting nucleic acid sequences with high specificity through base pairing
• Silencing, correcting splicing, degrading RNA, or replacing missing genetic information
• For diseases that are difficult to treat with traditional small molecules or proteins
• Often require chemical modification and specialized delivery systems to improve stability, uptake, and tissue targeting
• Can have really long half lives

What counts as a biologic?

• Biologics are medicines derived from living systems or their components.
• Proteins
• Genes
• Cells
• Their identity is tied to both molecular structure and manufacturing process.
• Many difficult diseases are now treated with biologic medicines.

Why biologics are powerful - and difficult

• Powerful: high specificity and access to previously hard-to-drug biology.
• Difficult: complex production, cold chain, immunogenicity, and batch
comparability.
• Analytics, QA/QC, and comparability are central, not peripheral.

What are some production hosts for protein drugs?

• Bacteria are fast and inexpensive but limited for complex folding and
glycosylation.
• Yeast offers scalable fermentation with some eukaryotic processing capacity.
• Mammalian cells are best for complex secreted and glycosylated biologics.
• Host choice is part of product design, not just manufacturing convenience

What are enzyme replacement therapies?

• ERT works best when a defined enzyme deficiency causes disease.
• Repeated dosing supplements or replaces the missing biochemical activity.
• Targeted delivery to the correct tissue or compartment is often the key
challenge.
• This is a classic supplementation strategy using a recombinant protein.

What are recombinant hormones?

• Insulin, growth hormone, and erythropoietin illustrate different clinical uses.
• Small concentration changes can cause large physiological effects.
• Recombinant production enabled cleaner supply and broader access.
• Half-life engineering and glycosylation strongly affect performance.

What are monoclonal antibodies?

• Antibodies bind targets with very high specificity.
• They can block ligands, block receptors, recruit immunity, or deliver cargo.
• Platform engineering tunes affinity, Fc function, and half-life.
• They are one of the clearest commercial success stories in therapeutic biotechnology.

What are immune modulators and cytokines?

• Interferons and interleukins can amplify or redirect immune responses.
• They are extremely potent but can have broad systemic effects.
• Their clinical value depends heavily on dose, schedule, and patient selection.
• They highlight the thin line between therapeutic stimulation and toxicity.

What are vaccines?

• Preventive vaccines train immunity before disease or
exposure causes damage.
• Therapeutic vaccines aim to reshape immunity after
disease is already present.
• Both rely on antigen design, formulation, and immune
context.
• Recombinant DNA and nucleic-acid platforms widened the design space for both

What are vaccine modalities?

Organic vesicular

Live/Attenuated

Synthetic Vesicular

Nucleic acid

Subunit

Conjugates

What is recombinant subunit vaccine production?

• A pathogen-derived antigen is expressed in a production host.
• The antigen is purified and formulated, often with an adjuvant.
• This approach avoids using the whole pathogen in the final product.
• Tradeoff: subunit antigens often need help to generate strong durable immunity.