L30 - New & Emerging Drug Technologies
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What does a mutation in DNA result in?
Defective protein requires for normal cell function = causes disease
What are some diseases are exacerbated by?
Increased levels of particular proteins
What can sub-physiological levels of protein be overcome by?
Delivering exogenous protein
What can nucleic acids be used as?
Treatment in all scenearios
What does therapeutic protein overcome?
Difficulties of producing & purifying recombinant proteins - getting patient’s cells to do it - transicent - repeated injections of gene/vector requires
What is siRNA? What does it do?
Small interfering NRA - knocks down gene expression if sequence is known
What are advantages of siRNA?
• readily designed • readily synthesised
What is miRNA? What is it derived from?
Micro RNA - genes that specifically code miRNAs (not proteins
What are miRNA important in?
Regulating gene expression (1/3 of genes)
What are advantages of miRNA?
• dont cause mRNA destructions (repress or destabilise) • strong evidence of involvement in diseases states (inc. cancer)
What can be delivered to cells to replace missing miRNAs?
DNA coding underexpressed or missing miRNAs
What can overexpressed miRNAs be inhibited by?
Anti-miRNAs - complementary nucleotides that bind to the problem miRNA
What are RNA vaccines?
• viral mRNA absorbed by cells • expressed on surface • labelled as foreign cells
What is cell therapy?
Delivery of cells to the patient to correct disease or damge - may be combined with genetic strategies (secrete therapeutic protein, reprogramming immune cells)
What is strimvelis? What does it treat?
First ex vivo stem cell gene therapy - treats severe combined immunodeficiency cause by adenosine deaminase deficiency - autologoes CD34+ cells expressing functional ADA - (rare)
How are cell therapies with CAR T cells done?
• remove blood from patient (get T cells) • make CAR T cells in lab • grow millions • infuse CAR T cells into patient • CAR T cells bind to cancer cells, killing them
What are approved CAR T cell therapies?
• kymriah • yescarta • tecartus • breyanzi • ABECMA • carvykti
What are emerging cell therapies?
• TCR-T cells • CAR-M • CAR-NK cells
How do CAR T cells work?
• recognise antigen on tumour cell • causes transcription of T cell effector function = perforin and granzyme release
What was combination cell-gene therapy?
• trialed in 56 patients • mesenchymal stem cells transfected with gene (TRAIL) • off the shelf treatment • scaling up cell culture (key) • funded through the biomedical catalyst (MRC and Innovate UK)
What are current approaches to nucleic acid therapy like?
Often transient - varying degrees of success
What is gene editing?
Permanently editing the genome to correct a defect, knocking down a specific gene/activating a gene
What are ways of gene editing?
Break in double strand break - gene disruption - gene correction - gene insertion
What is an example of gene editing? What does it do?
CRISPR/Cas9 (system from bacteria can be used to edit DNA) - modifies genes in human cells in vitro and in vivo - used to inactivate, correct and insert genes