Therapeutic Interventions

Gene therapy

Involves introduction, alterations or silencing of genes within a patient's cells to treat or prevent disease

What is the aim of gene therapy?

-To correct genetic defects

-Modify gene expression

-Enhance the body's ability to fight specific diseases

Gene addition

Introducing a new, functional gene to compensate for a nonfunctional or mutated gene

Gene silencing

Inhibiting the expression of a specific gene

Often used to suppress disease-causing genes

Gene editing

Directly modifying the DNA sequence within a patient's cells to correct genetic abnormalities

What are some inherited genetic disorders that can be treated using gene therapy?

Cystic fibrosis

Muscular dystrophy

Haemophilia

What is the main aim of gene therapy in treating genetic disorders?

Addresses the root cause of these disorders by replacing or repairing the defective gene

How can gene therapy be used in cancer?

Target or destroy cancer cells

Enhance immune system to respond

Inhibit tumour growth

How can gene therapy be used in infectious disease?

Holds promise for combining viral infections such as HIV

Modify immune cells to resist viral replication

What can be used to deliver gene therapy?

Viral and non-viral vectors

What are the potential risks of gene therapy?

Unintended immune responses

Off-target effects

Long-term monitoring of gene expression

What are the ethical consideration of gene therapy?

Related to germline editing

Consent

Equitable access to gene therapy

RNA interference (RNAi)

Conserved cellular mechanism involved in the regulation of gene expression through degradation or inhibition of specific mRNA molecules

What is the main role of RNAi?

Crucial post-transcriptional gene regulation mechanism in eukaryotic cells

What can RNAi be used for?

Cellular processes:

-development

-immunity

-response to external stimuli

Double-stranded RNA

Triggers RNAi pathway

From exogenous sources or from hairpin loop in cellular RNA

Dicer enzyme

Cleaves long dsRNA into short interfering RNA (siRNA) or microRNA

Key effectors of RNAi

RNA-Induced Silencing Complex (RISC)

siRNA or miRNA is loaded onto RISC complex

Guide it to the target mRNA

What does perfect base pairing between the siRNA and target mRNA lead to?

mRNA cleavage and subsequent degradation

What happens when miRNA bind imperfectly to the target mRNA?

Leads to translational repression or mRNA degradation

RNAi and gene silencing

Plays a role in silencing expression patterns in response to environmental cues or developmental stages

Developmental processes using RNAi

Regulates expression of genes involved in embryonic development, tissue differentiation and organogenesis

Immune response from RNAi

Modulates the expression of immune-related genes

Influence cellular response to pathogens and foreign nucleic acids

Pharmacogenetics

Study of how genetic variations influence an individuals response to drugs

Aim of pharmacogenetics

Personalise medication selection and dosing based on individuals genetic makeup

Single Nucleotide Polymorphisms (SNPs) and pharmacogenetics

Common variations in single nucelotides can impact drug metabolism enzymes, transporters and drug targets

Copy number variations (CNVs) and pharmacogenetics

Structural variations may affect gene dosage and protein expression levels

Influence drug response

Cytochrome P450 enzymes (CYP) and pharmacogenetics

Genetic polymorphisms in CYP genes can significantly alter the metabolism of wide range of drugs affecting their efficacy and toxicity

What are 2 examples of drug-metabolising enzymes that impact drug metabolism?

-UDP-glucuronosyltransferase (UGTs)

-Thiopurine S-methyltransferase (TPMT)

Nanomedicine

Application of nanotechnology for medical purposes

What size are nanoparticles?

1 to 100 nanometers

Provide high surface area to volume ratio

What can nanoparticles be fused with?

Ligands

Antibodies

Targeting moieties

What is the importance of nanoparticles being bound to other molecules?

Achieve selective interactions with specific cells or tissues

Enable targeted drug delivery and imaging

Enhanced Permeability and Retention (EPR) Effect

Nanoparticles can exploit the leaky vasculature of tumours for passive accumulation

Leads to improved drug delivery

Controlled release of nanoparticles

Sustained and controlled release

Enhances efficacy and reducing systemic side effects

Where are nanoparticles used as contrast agents?

MRI

CT

Optical imaging

Multimodal imagining using nanoparticles

Designed to exhibit multi-functionality

Allow for simultaneous imaging for comprehensive diagnostic information

Theranostics

Integrating imaging and therapeutic functionalities into a single nanoparticle for personalised cancer treatment and monitoring

Can nanoparticles cross the blood brain barrier?

Yes

Looked at to treat neurological conditions such as brain tumours and neurodegenerative diseases

Nanoparticles role in tissue engineering

Play a role in scaffolds and delivery systems for regenerative medicine applications