Therapeutic Interpretations & Gene Therapy

Therapeutic Interpretations

• Therapeutic Interpretations are explored by Dr Temba Mudariki

Gene Therapy

• Gene therapy involves introducing, altering, or silencing genes to treat or prevent diseases
• The aim is to correct genetic defects, modify gene expression, or enhance the body's ability to fight specific diseases
• Gene therapy emerged in the 1970s
• Significant advancements have improved understanding of genetic diseases, leading to gene-based treatments
• Gene addition is introducing a new, functional gene to compensate for a nonfunctional or mutated gene
• Gene silencing is inhibiting the expression of a specific gene, often used to suppress disease-causing genes
• Gene editing is directly modifying the DNA sequence within a patient's cells to correct genetic abnormalities
• It offers potential treatments for inherited genetic disorders like cystic fibrosis, muscular dystrophy, and hemophilia
• Gene therapy aims to address the root cause of these disorders by replacing or repairing the defective gene
• In cancer treatments, gene therapy can target and destroy cancer cells, enhance the immune system's response, or inhibit tumor growth
• It holds promise for combating viral infections like HIV by modifying immune cells to resist viral replication
• It is being explored for neurodegenerative disorders like Parkinson's and Alzheimer's disease
• Research is being conducted into treating cardiovascular diseases like heart failure and inherited heart disorders
• Efficient and targeted delivery of therapeutic genes remains a significant challenge
• Viral and non-viral vectors are used for delivering therapeutic genes, each with its advantages and limitations
• Potential risks include unintended immune responses, off-target effects, and long-term monitoring of gene expression
• Ethical issues related to germline editing, consent, and equitable access to gene therapy need to be considered
• Regulatory agencies play a crucial role in evaluating the safety, efficacy, and ethical implications of gene therapy products
• Gene therapy holds immense potential for revolutionizing the treatment of genetic disorders and acquired diseases
• Ongoing research and technological advancements are continually expanding the scope of gene therapy applications

RNA Interference

• RNA interference (RNAi) is a conserved cellular mechanism in gene expression regulation by degrading or inhibiting mRNA molecules
• It serves as a crucial post-transcriptional gene regulation mechanism in eukaryotic cells
• RNAi was first discovered in the early 1990s, revolutionizing the understanding of gene regulation
• RNAi plays a fundamental role in various cellular processes, including development, immunity, and response to external stimuli
• The RNAi pathway is triggered by double-stranded RNA (dsRNA) from exogenous sources or hairpin loops
• Dicer cleaves long dsRNA into short interfering RNAs (siRNAs) or microRNAs (miRNAs), which are key effectors
• siRNA or miRNA is loaded onto the RISC complex, guiding it to the target mRNA
• Perfect base pairing between the siRNA and the target mRNA leads to mRNA cleavage and degradation
• miRNAs inaccurately bind to the target mRNA, leading to translational repression or mRNA degradation
• RNAi is critical in silencing the expression of specific genes, allowing cells to fine-tune gene expression patterns
• Regulates the expression of genes involved in embryonic development, tissue differentiation, and organogenesis
• it modulates the expression of immune-related genes involved in the cellular response to pathogens
• RNAi-based therapeutics can be treating viral infections, cancer, and genetic disorders through selective gene silencing
• Ongoing research focuses on understanding the regulatory networks governed by RNAi and its crosstalk with cellular pathways
• Efficient and targeted delivery to specific cell types and tissues, while minimizing off-target effects, are key challenges in therapeutics
• Clinical translation of RNAi-based therapeutics requires careful consideration of safety, off-target effects, and long-term monitoring

Pharmacogenetics

• Pharmacogenetics studies how genetic variations influence an individual's response to drugs, including metabolism, efficacy, and adverse effects
• It aims to personalize medication selection and dosing based on an individual's genetic makeup
• The field has evolved from early observations of genetic differences in drug responses to the era of personalized healthcare
• Single Nucleotide Polymorphisms (SNPs) are common nucleotide variations that impact drug metabolism enzymes, transporters, and targets
• Copy Number Variations (CNVs) may affect gene dosage, protein expression, and drug response are structural variations
• Genetic polymorphisms in CYP genes can alter the metabolism of a wide range of drugs, affecting their efficacy and toxicity
• Variations in UDP-glucuronosyltransferases (UGTs) and thiopurine S-methyltransferase (TPMT) impact drug metabolism
• Genetic variations in drug targets, such as receptors or enzymes, can influence drug binding affinity and therapeutic response
• Polymorphisms in drug transporters, including ATP-binding cassette (ABC) transporters, can affect drug absorption, distribution, and excretion
• Pharmacogenetic testing enables identification of individuals with atypical responses, guiding alternative drug selection or personalized dosing
• Anticipating genetic predispositions to adverse reactions allows for proactive measures to minimize severe side effects
• Understanding genetic variability in drug response facilitates the selection of medications and are effective based on genetic profiles
• Challenges include integrating pharmacogenetic testing into routine clinical care, interpreting test results, and ensuring accessibility and equity
• Regulatory agencies evaluate the validity and utility of pharmacogenetic tests
• Ethical considerations include patient autonomy and the responsible use of genetic information
• Education of healthcare professionals and patients is needed to facilitate informed decision-making and maximize the benefits of personalized medicine

Nanomedicine

• It applies nanotechnology for diagnosis, drug delivery, imaging, and therapy
• It harnesses the unique properties of nanoparticles to develop innovative medical solutions
• This field has rapidly evolved, driven by advancements in nanotechnology, material science, and biomedical engineering
• Nanoparticles range from 1 to 100 nanometers in size, providing a high surface area-to-volume ratio
• This enhances their interactions with biological systems
• Nanoparticles can be functionalized with ligands, antibodies, or targeting moieties
• Achieves selective interactions with specific cells or tissues, enabling targeted drug delivery and imaging
• Nanoparticles can exploit the leaky vasculature of tumors for passive accumulation and improved drug delivery to cancerous tissues
• Nanoparticles enable sustained and controlled release of therapeutic agents, enhancing their efficacy and reducing systemic side effects
• Nanoparticles can serve as contrast agents for imaging modalities like MRI, CT, and optical imaging
• This provides enhanced visualization of tissues and disease markers
• Nanoparticles can be designed to exhibit multi-functionality, allowing for simultaneous imaging for comprehensive diagnostic information
• Nanoparticles enable targeted delivery of chemotherapeutic agents to tumor sites, minimizing damage to healthy tissues
• Theranostics integrates imaging and therapeutic functionalities into a single nanoparticle for personalized cancer treatment and monitoring
• Nanoparticles are being explored for delivering drugs across the blood-brain barrier to treat neurological conditions
• Nanoparticles play a role in scaffolds and delivery systems for regenerative medicine applications, promoting tissue regeneration and repair
• Understanding the interactions of nanoparticles with biological systems is crucial to ensure biocompatibility and minimize toxic effects
• Nanomedicine products are subject to rigorous evaluation by regulatory agencies to ensure safety, efficacy, and quality before clinical use
• Discussions surrounding ethical considerations, public perception, and equitable access to nanomedicine are essential