Introduction to Pharmaceutical Biotechnology PDF

Introduction to Pharmaceutical Biotechnology Dr Ala AbuHammad, PhD ([email protected] ) WHAT IS PHARMACEUTICAL BIOTECHNOLOGY?  Definition of Biotechnology: The use of living organisms, cells, or biological systems to develop products that improve human health and quality...

Introduction to Pharmaceutical Biotechnology Dr Ala AbuHammad, PhD ([email protected] ) WHAT IS PHARMACEUTICAL BIOTECHNOLOGY?  Definition of Biotechnology: The use of living organisms, cells, or biological systems to develop products that improve human health and quality of life.  Pharmaceutical Biotechnology: The application of biotechnology in drug development, production, and healthcare solutions. Dr Ala Abuhammad, PhD Oct-24 11 BIOTECHNOLOGY – A COCKTAIL OF BIOLOGY AND TECHNOLOGY?  Biotechnology can be called as cocktail of Biology and Technology.  The integrated use of biochemistry, microbiology and engineering sciences in order to achieve technological application of the capabilities of microorganisms, cultured tissue, cells, and parts their of [The European Federation of Biotechnology (EFB), 1981; O'Sullivan, 1981]. Dr Ala Abuhammad, PhD Oct-24 12 BIOTECHNOLOGY – REAL-WORLD APPLICATIONS: COVID-19 Vaccines Recombi- mABs nant DNA Medical examples Antibiotics (e.g. Penicillin) Gene Antibiotics Therapy (Penicillin) Diagn- ostics PCR testing Dr Ala Abuhammad, PhD Oct-24 13  CONT’D  Pfizer-BioNTech (Comirnaty) and Moderna (Spikevax) were the first COVID-19 vaccines approved in many countries and have shown high efficacy in preventing severe disease.  These vaccines use messenger RNA (mRNA), a type of genetic material that instructs cells to produce the spike protein found on the surface of the SARS-CoV-2 virus (the virus that causes COVID-19).  The mRNA is delivered into human cells, usually by lipid nanoparticles, which protect the fragile RNA. Once inside, the cells use the mRNA to make copies of the spike protein.  The immune system recognizes the spike protein as foreign and generates an immune response, including the production of antibodies and memory cells.  mRNA vaccines do not use live virus, so there is no risk of getting COVID-19 from the vaccine. Dr Ala Abuhammad, PhD Oct-24 14 CONT’D  Insulin (Humulin®)  Produced through recombinant DNA technology, Humulin was the first biotechnology- derived medicine approved by the FDA. It’s created by inserting the human insulin gene into bacteria (such as E. coli) to produce insulin on a large scale. This product revolutionized diabetes management, replacing animal-derived insulin with a purer and more effective version.  Erythropoietin (EPO) (Epogen®, Procrit®)  EPO is produced using recombinant DNA technology in mammalian cell lines, such as Chinese hamster ovary (CHO) cells, to mimic the natural hormone that stimulates red blood cell production.  It is crucial for patients who cannot produce enough erythropoietin, improving quality of life and reducing the need for blood transfusions.  Uses: Anemia treatment (especially in chronic kidney disease and cancer patients) Dr Ala Abuhammad, PhD Oct-24 15 CONT’D  Monoclonal Antibodies examples  Humira®  Monoclonal antibody therapy, where humanized antibodies target specific proteins involved in the inflammatory process (e.g., TNF-α in Humira's case).  Humira was one of the world’s best-selling drugs, demonstrating the power of monoclonal antibodies in targeting specific disease pathways with fewer side effects.  Uses: Autoimmune diseases (rheumatoid arthritis, Crohn’s disease, psoriasis)  Herceptin® (Trastuzumab)  A monoclonal antibody that targets the HER2 receptor, which is overexpressed in certain breast cancer cells, inhibiting their growth.  Herceptin is a breakthrough targeted therapy that specifically treats HER2-positive breast cancer, significantly improving survival rates for patients with this type of cancer.  Uses: Breast cancer treatment (HER2-positive breast cancer. Dr Ala Abuhammad, PhD Oct-24 16 CONT’D  Biotechnological applications in antibiotic production  Beta-lactam Antibiotics (e.g. Penicillin)  Originally discovered from the Penicillium mold, biotechnology has improved the fermentation processes and genetic engineering of strains to increase yield and create semi-synthetic derivatives, such as amoxicillin and cephalosporins, that are effective against a broader range of bacteria.  Glycopeptide Antibiotics (e.g. Vancomycin)  Description: A critical antibiotic used to treat serious infections caused by Gram- positive bacteria, including MRSA. Advances in biotechnology have led to improved production methods to meet increasing demand. Dr Ala Abuhammad, PhD Oct-24 17 CONT’D  Biotechnological applications in antibiotic production  Aminoglycoside Antibiotics (e.g. Gentamicin)  Produced by the bacterium Micromonospora purpurea, gentamicin is effective against a variety of bacterial infections. Biotechnology enhances the fermentation process to optimize yield and purity.  Lipopeptide Antibiotics (e.g. Daptomycin)  A lipopeptide antibiotic derived from the bacterium Streptomyces roseosporus, it is used to treat complicated skin infections and bacteremia. Biotechnology has allowed for the production of this compound in larger quantities. Dr Ala Abuhammad, PhD Oct-24 18 CONT’D  Biotechnological applications in antibiotic production  Aminoglycoside Antibiotics (e.g. Gentamicin)  Produced by the bacterium Micromonospora purpurea, gentamicin is effective against a variety of bacterial infections. Biotechnology enhances the fermentation process to optimize yield and purity.  Lipopeptide Antibiotics (e.g. Daptomycin)  A lipopeptide antibiotic derived from the bacterium Streptomyces roseosporus, it is used to treat complicated skin infections and bacteremia. Biotechnology has allowed for the production of this compound in larger quantities. Dr Ala Abuhammad, PhD Oct-24 19 CONT’D  Notable approved gene therapy applications  Luxturna (Voretigene Neparvovec)  Condition Treated: Inherited retinal dystrophy (caused by mutations in the RPE65 gene).  How It Works: Luxturna delivers a functional copy of the RPE65 gene directly to retinal cells, allowing them to produce a protein necessary for vision, potentially restoring sight or slowing vision loss.  Approved by FDA (2017).  Zolgensma (Onasemnogene Abeparvovec)  Condition Treated: Spinal muscular atrophy (SMA), a severe genetic disorder leading to muscle weakness and loss of motor function.  How It Works: Zolgensma introduces a working copy of the SMN1 gene to replace the faulty or missing gene, allowing for normal production of the SMN protein, which is critical for motor neuron survival.  Approved by FDA (2019). Dr Ala Abuhammad, PhD Oct-24 20 CONT’D  Notable approved gene therapy applications  Zynteglo (Betibeglogene Autotemcel)  Condition Treated: Beta-thalassemia, a blood disorder that reduces the production of hemoglobin.  How It Works: Zynteglo adds functional copies of the HBB gene into a patient’s hematopoietic stem cells, enabling them to produce enough hemoglobin, reducing or eliminating the need for blood transfusions.  Approved by: EMA (2019) and FDA (2022). Dr Ala Abuhammad, PhD Oct-24 21 CONT’D  Diagnostics:  1. PCR (Polymerase Chain Reaction)  PCR amplifies specific DNA sequences, making it possible to detect even trace amounts of genetic material.  COVID-19 testing: Detects viral RNA from SARS-CoV-2.  Genetic mutations: Identifies mutations in genes for diseases like cystic fibrosis and cancer.  Infectious diseases: Detects pathogens like HIV, hepatitis, and tuberculosis.  2. ELISA (Enzyme-Linked Immunosorbent Assay)  ELISA uses antibodies and color change to detect the presence of specific proteins or antibodies in a sample.  HIV testing: Identifies HIV antibodies.  Hormonal assays: Measures hormones like insulin or thyroid hormones.  Allergy testing: Detects allergen-specific IgE antibodies.  3. Next-Generation Sequencing (NGS)  NGS sequences large amounts of DNA quickly, allowing for comprehensive genomic analysis.  Cancer diagnostics: Detects mutations across multiple cancer-related genes.  Prenatal screening: Identifies genetic abnormalities like Down syndrome in fetuses.  Rare genetic diseases: Helps in the diagnosis of rare inherited disorders. Dr Ala Abuhammad, PhD Oct-24 22 CONT’D  4. CRISPR-Based Diagnostics  CRISPR technology can detect specific genetic sequences by using a guide RNA to target and cleave DNA or RNA from pathogens or mutated genes.  COVID-19 rapid tests: CRISPR-based systems like SHERLOCK can detect the SARS-CoV-2 virus.  Point-of-care diagnostics: Potential for diagnosing infectious diseases like Zika or dengue quickly.  5. Microarray Technology  How It Works: DNA microarrays detect the expression of thousands of genes at once by hybridizing sample DNA to specific probes on a chip.  Cancer gene profiling: Identifies gene expression changes in tumor cells.  Pharmacogenomics: Assesses genetic variants that affect drug metabolism, allowing personalized medicine.  6. Biosensors  Biosensors detect biological molecules using a combination of a biological element (such as enzymes or antibodies) and a physical transducer.  Blood glucose monitoring: Detects glucose levels in diabetic patients.  Point-of-care diagnostics: Rapid tests for infections like malaria or urinary tract infections. Dr Ala Abuhammad, PhD Oct-24 23 CONT’D  7. Immunohistochemistry (IHC)  IHC uses antibodies to detect specific proteins in tissue sections, providing visual evidence of protein expression.  Cancer diagnostics: Detects biomarkers like HER2 in breast cancer.  Autoimmune disease diagnosis: Identifies autoantibodies in diseases like lupus.  8. Mass Spectrometry  How It Works: Mass spectrometry measures the mass of molecules, often used for protein identification and quantification.  Proteomics: Identifies protein biomarkers for diseases.  Drug testing: Detects metabolites or contaminants in biological samples.  9. Flow Cytometry  Flow cytometry measures the physical and chemical characteristics of cells in a fluid stream using lasers.  Leukemia and lymphoma diagnosis: Detects abnormal cell populations.  HIV monitoring: Measures CD4+ T cell levels in HIV patients. Dr Ala Abuhammad, PhD Oct-24 24 CONT’D  10. Metabolomics  Analyzes small molecules (metabolites) in biological systems (i.e. using mass spectrometry or NMR), measuring their levels reflecting the alterations in associated metabolic pathways.  Cancer and diabetes diagnosis: Detects metabolite biomarkers in the blood or urine.  Nutritional status and drug metabolism: Monitors metabolic response to therapies or diets.  Personalized medicine: Tailors treatment based on individual metabolic profiles. Dr Ala Abuhammad, PhD Oct-24 25 HOW WILL BIOTECHNOLOGY CHANGE OUR LIVES IN THE YEARS AHEAD?! Advancement How It Will Change Lives Examples Customized treatments based on genetics, improving Targeted cancer therapies like trastuzumab Personalized Medicine effectiveness and reducing side effects. (Herceptin) for HER2-positive breast cancer. Cures for genetic diseases by correcting defective genes Zolgensma for spinal muscular atrophy Advanced Gene Therapy (e.g., using CRISPR technology). (SMA). Tissue and organ regeneration for transplants, solving Stem cell therapies for heart regeneration, Regenerative Medicine organ donor shortages. lab-grown organs. More targeted therapies, like immunotherapy, offering CAR T-cell therapy for leukemia and Improved Cancer Treatments more effective and less harmful treatments. lymphoma. Early detection of diseases through advanced molecular Liquid biopsies for early cancer detection, Enhanced Diagnostics diagnostics, leading to better outcomes. genetic testing for predispositions. Faster development of vaccines (e.g., mRNA vaccines), Pfizer-BioNTech and Moderna COVID-19 Vaccine Innovation improving response to pandemics. vaccines. More efficient production of biopharmaceuticals, Insulin production using recombinant DNA Biomanufacturing lowering costs and increasing accessibility. technology. Dr Ala Abuhammad, PhD Oct-24 26 BIOTECHNOLOGY – REAL-WORLD APPLICATIONS: Biodegrad able Plastics Forensic Biofuels Science Beyond Pharmacy Genetica Biorem- lly Modified ediation Crops (GMOs): Aquacul ture Dr Ala Abuhammad, PhD Oct-24 27 CONT’D  Biofuels: Production of ethanol from crops like corn and sugarcane, or the use of algae to produce sustainable biofuels.  Bioplastics: Polylactic acid (PLA) bioplastics are produced using fermented plant sugars, offering a more sustainable alternative to petroleum-based plastics.  Genetically Modified Crops (GMOs): Crops like Bt corn and Roundup Ready soybeans are engineered for pest resistance and herbicide tolerance, improving yields and reducing pesticide use.  Bioremediation: Using microorganisms to clean up oil spills, heavy metals, or pollutants in the environment (e.g., the Exxon Valdez oil spill cleanup).  DNA Fingerprinting: Biotechnology is used in criminal investigations to match DNA samples, identify suspects, and solve cases.  Genetically Modified Fish: AquAdvantage salmon is an example of a genetically modified fish that grows faster than its wild counterpart, enhancing food production in aquaculture. AquAdvantage salmon is a genetically engineered fish, a GE Atlantic salmon developed by AquaBounty Technologies in 1989. The typical growth hormone-regulating gene in the Atlantic salmon was replaced with the growth hormone-regulating gene from Pacific Chinook salmon, with a promoter sequence from ocean pout. Dr Ala Abuhammad, PhD Oct-24 28 HOW WILL BIOTECHNOLOGY CHANGE OUR LIVES IN THE YEARS AHEAD?! Advancement How It Will Change Lives Examples Genetically modified crops with enhanced yield, disease Bt cotton (pest resistance), Golden Rice Agricultural Biotechnology resistance, and nutritional value. (vitamin A enrichment). Environmental Bioremediation techniques to clean up polluted Use of bacteria to clean oil spills, Biotechnology environments, restoring ecosystems. phytoremediation with plants. Sustainable production of biofuels and bioplastics, reducing Bioethanol from corn, bioplastics from plant Industrial Biotechnology dependence on fossil fuels. materials (e.g., PLA). Improved food safety and nutritional content through Probiotics in yogurt, fortified foods (e.g., Food Biotechnology fermentation and biofortification. vitamin-enriched cereals). Enhanced breeding and health management practices Genetically modified salmon (faster Animal Biotechnology leading to better livestock productivity. growth), disease-resistant chickens. Data analysis for better understanding of biological Genomic data analysis for crop Bioinformatics processes and faster innovation in research. improvement, drug discovery platforms. Production of chemicals and materials from renewable Production of enzymes for detergents, Biomanufacturing resources, leading to more sustainable industry practices. biodegradable materials from microbes. Dr Ala Abuhammad, PhD Oct-24 29 WHY BIOTECHNOLOGY?  Sometimes the only way to produce certain products: Biotechnology enables the production of complex biological molecules, like insulin or monoclonal antibodies, that are challenging to synthesize chemically.  High selectivity (targeting): Biotechnological processes often yield highly specific products, while reducing unwanted by-products.  Fewer by-products: Biotechnology can create cleaner processes with fewer waste materials compared to traditional chemical synthesis.  Mild reactor conditions: Biotechnology operates under moderate conditions (e.g., temperature, pressure), making it more energy-efficient and safer.  Process intensification: In biotechnology, a single biological process can replace multiple chemical steps, streamlining production and reducing costs. Dr Ala Abuhammad, PhD Oct-24 30 WHY BIOTECHNOLOGY?  Sustainability: o Reduced energy consumption: Biotechnological processes typically operate under mild conditions, cutting down energy use. o Reduced CO₂ emissions: Use of renewable resources, like biomass, helps lower greenhouse gas emissions. o Reduced waste: Many biotech processes generate biodegradable by-products, minimizing environmental impact.  Economics (long term): o Cost of fossil-based products: As crude oil prices rise, fossil-based chemical processes become more expensive. o Use of renewable raw materials: Biotechnology can utilize sustainable sources like agricultural residues, energy crops, and algae, making it economically viable in the long run. Dr Ala Abuhammad, PhD Oct-24 31 TYPES OF BIOTECHNOLOGY?  The "color classification" (e.g., Red, Green, White, Blue, etc.) is a widely used, informal framework to categorize different fields of biotechnology based on their applications.  This classification has been adopted by educators, professionals, and various organizations to make it easier to discuss and understand the diverse applications of biotechnology. Dr Ala Abuhammad, PhD Oct-24 32  BIOTECHNOLOGY APPLICATIONS – ETHICAL CONSIDERATIONS & IMPLICATIONS the key ethical considerations in biotechnology applications & their implications  Genetic Privacy  Concerns about misuse of genetic information and discrimination based on genetic data.  Example: Genetic testing revealing predispositions to diseases.  Biodiversity Loss  Genetic modification of crops and animals may reduce biodiversity and disrupt ecosystems.  Example: Monoculture practices in genetically modified crops.  Animal Welfare  Ethical treatment of animals used in research and biotechnology applications.  Example: Concerns over genetically engineered animals for food production.  Access and Equity  Ensuring equitable access to biotechnological advancements to prevent disparities.  Example: Access to gene therapies and expensive treatments. Dr Ala Abuhammad, PhD Oct-24 33 BIOTECHNOLOGY APPLICATIONS – ETHICAL CONSIDERATIONS & IMPLICATIONS  Informed Consent  Patients and subjects must be informed about the risks and benefits of biotechnological procedures.  Example: Genetic testing for inherited conditions without proper counseling.  Dual Use Concerns  Biotechnology can be used for harmful purposes, such as bioweapons or unethical research.  Example: Potential misuse of CRISPR technology for creating harmful pathogens.  Food Safety and Labeling  Ethical concerns surrounding labeling of genetically modified foods and consumer choice.  Example: GMO labeling initiatives and public debate over food safety.  Human Enhancement  Ethical dilemmas regarding biotechnology use for non-therapeutic enhancements.  Example: Genetic modification for enhanced physical or cognitive traits. Dr Ala Abuhammad, PhD Oct-24 34