👩‍🔬Intro to Biotechnology Unit 9 – Biotech in Medicine and Pharmaceuticals

Key Concepts and Terminology

• Biotechnology involves using living organisms or biological systems to develop products and processes that benefit human health and medicine
• Pharmaceuticals are drugs or medicines used to diagnose, cure, treat, or prevent disease
• Biopharmaceuticals are pharmaceuticals produced using biotechnology techniques (recombinant DNA, monoclonal antibodies)
• Drug discovery is the process of identifying and validating new drug targets and developing new therapeutic compounds
• Clinical trials are research studies that evaluate the safety and efficacy of new drugs or medical treatments in human subjects
  • Consist of four phases (Phase I, II, III, and IV) with increasing numbers of participants and complexity
• Personalized medicine tailors medical treatments to an individual's genetic profile, lifestyle, and environment for more targeted and effective therapies
• Gene therapy involves introducing functional genes into cells to replace defective or missing genes and treat genetic disorders

Historical Context and Milestones

• In 1928, Alexander Fleming discovered penicillin, marking the beginning of the antibiotic era and revolutionizing the treatment of bacterial infections
• The 1953 discovery of the double helix structure of DNA by James Watson and Francis Crick laid the foundation for modern biotechnology and genetic engineering
• Recombinant DNA technology, developed in the 1970s, allowed the manipulation and transfer of genes between organisms, enabling the production of human proteins in bacteria (insulin)
• The first genetically engineered drug, human insulin produced in E. coli, was approved by the FDA in 1982
• The Human Genome Project, completed in 2003, sequenced the entire human genome, providing valuable insights into the genetic basis of diseases and paving the way for personalized medicine
• In 2017, the FDA approved the first gene therapy for an inherited disease (Luxturna for retinal dystrophy) and the first CAR T-cell therapy for cancer (Kymriah for leukemia)

Biotechnology Techniques in Medicine

• Recombinant DNA technology enables the production of therapeutic proteins (insulin, growth hormone) in genetically modified organisms
• Monoclonal antibodies, produced by hybridoma technology, are highly specific antibodies used for targeted drug delivery, cancer therapy, and diagnostic tests
  • Examples include Herceptin for breast cancer and Humira for rheumatoid arthritis
• Polymerase chain reaction (PCR) amplifies small amounts of DNA for genetic testing, disease diagnosis, and forensic analysis
• CRISPR-Cas9 is a precise gene-editing tool that allows the modification of DNA sequences to correct genetic defects or enhance desired traits
• Stem cell therapy utilizes the regenerative potential of stem cells to repair or replace damaged tissues and treat diseases (leukemia, Parkinson's)
• Tissue engineering combines cells, scaffolds, and growth factors to create functional tissue substitutes (artificial skin, cartilage)

Drug Discovery and Development

• Target identification involves identifying and validating molecular targets (receptors, enzymes) that play a role in disease pathology
• High-throughput screening (HTS) rapidly tests large libraries of compounds against a target to identify potential drug candidates
• Lead optimization improves the potency, selectivity, and pharmacokinetic properties of lead compounds through medicinal chemistry
• Preclinical studies assess the safety and efficacy of drug candidates in animal models before human trials
• Clinical trials evaluate the safety and efficacy of new drugs in human subjects, progressing from small Phase I studies to large Phase III trials
  • Phase IV post-marketing surveillance monitors long-term safety and effectiveness after FDA approval
• Bioinformatics and computational tools aid in drug design, target prediction, and data analysis throughout the drug discovery process

Gene Therapy and Personalized Medicine

• Gene therapy introduces functional genes into cells to replace defective or missing genes and treat genetic disorders (cystic fibrosis, sickle cell anemia)
  • Viral vectors (adenovirus, retrovirus) are commonly used to deliver therapeutic genes into target cells
• Personalized medicine tailors medical treatments to an individual's genetic profile, lifestyle, and environment for more targeted and effective therapies
• Pharmacogenomics studies how genetic variations influence drug response and guides the selection of optimal drugs and doses for individual patients
• Genome sequencing and genetic testing identify disease-associated mutations and predict disease risk, enabling early intervention and preventive measures
• Targeted cancer therapies, such as small molecule inhibitors (Gleevec for leukemia) and antibody-drug conjugates (Kadcyla for breast cancer), specifically target cancer cells based on their molecular characteristics
• Regenerative medicine utilizes stem cells, tissue engineering, and gene therapy to repair, replace, or regenerate damaged tissues and organs

Ethical Considerations and Regulations

• Informed consent ensures that participants in clinical trials and genetic testing fully understand the risks, benefits, and implications of their involvement
• Privacy and confidentiality protect sensitive genetic information from unauthorized access and discrimination (Genetic Information Nondiscrimination Act)
• Equitable access to biotechnology-derived treatments and personalized medicine is essential to prevent widening health disparities
• Gene editing in human embryos raises ethical concerns about designer babies and the long-term consequences of modifying the human germline
• Regulation by the FDA, EMA, and other agencies ensures the safety, efficacy, and quality of biotechnology-derived products and therapies
  • Rigorous preclinical and clinical testing, manufacturing standards (Good Manufacturing Practices), and post-marketing surveillance
• Intellectual property rights (patents) incentivize innovation but may limit access to life-saving treatments in developing countries

Current Applications and Case Studies

• Recombinant human insulin (Humulin) has revolutionized diabetes management, providing a safer and more reliable alternative to animal-derived insulin
• Herceptin, a monoclonal antibody targeting HER2-positive breast cancer, has significantly improved survival rates and quality of life for patients
• Spinraza, an antisense oligonucleotide therapy for spinal muscular atrophy, has shown remarkable efficacy in improving motor function and survival in infants and children
• CAR T-cell therapy (Kymriah, Yescarta) has achieved impressive response rates in patients with relapsed or refractory blood cancers, offering hope for previously untreatable cases
• Luxturna, a gene therapy for inherited retinal dystrophy, has restored functional vision in patients with RPE65 mutations, demonstrating the potential of gene therapy for rare genetic diseases
• Personalized cancer vaccines, such as mRNA vaccines targeting patient-specific neoantigens, are being developed to stimulate anti-tumor immune responses and prevent cancer recurrence

Future Trends and Challenges

• CRISPR-based gene editing holds promise for treating a wide range of genetic diseases, but off-target effects and long-term safety need to be carefully evaluated
• Microbiome-based therapies, such as fecal microbiota transplantation and engineered probiotics, may offer new approaches to treating gastrointestinal disorders, metabolic diseases, and mental health conditions
• Artificial intelligence and machine learning will play an increasingly important role in drug discovery, precision medicine, and clinical decision support
  • AI-powered platforms can accelerate the identification of drug targets, predict drug-target interactions, and optimize clinical trial design
• Nanomedicine, utilizing nanoscale materials and devices for drug delivery and diagnostics, may enable more targeted and efficient therapies with reduced side effects
• Addressing the high cost and limited accessibility of biotechnology-derived treatments remains a major challenge, requiring innovative pricing models and global collaboration
• Ensuring the ethical and responsible development and application of biotechnology in medicine, particularly in areas such as gene editing and neurotechnology, will be critical for maintaining public trust and maximizing societal benefits