L30 - New & Emerging Drug Technologies

Question 1

What does a mutation in DNA result in?

Answer 1

Defective protein requires for normal cell function
= causes disease

Question 2

What are some diseases are exacerbated by?

Answer 2

Increased levels of particular proteins

Question 3

What can sub-physiological levels of protein be overcome by?

Answer 3

Delivering exogenous protein

Question 4

What can nucleic acids be used as?

Answer 4

Treatment in all scenearios

Question 5

What does therapeutic protein overcome?

Answer 5

Difficulties of producing & purifying recombinant proteins
- getting patient’s cells to do it
- transicent - repeated injections of gene/vector requires

Question 6

What is siRNA? What does it do?

Answer 6

Small interfering NRA
- knocks down gene expression if sequence is known

Question 7

What are advantages of siRNA?

Answer 7

• readily designed
• readily synthesised

Question 8

What is miRNA? What is it derived from?

Answer 8

Micro RNA
- genes that specifically code miRNAs (not proteins

Question 9

What are miRNA important in?

Answer 9

Regulating gene expression (1/3 of genes)

Question 10

What are advantages of miRNA?

Answer 10

• dont cause mRNA destructions (repress or destabilise)
• strong evidence of involvement in diseases states (inc. cancer)

Question 11

What can be delivered to cells to replace missing miRNAs?

Answer 11

DNA coding underexpressed or missing miRNAs

Question 12

What can overexpressed miRNAs be inhibited by?

Answer 12

Anti-miRNAs
- complementary nucleotides that bind to the problem miRNA

Question 13

What are RNA vaccines?

Answer 13

• viral mRNA absorbed by cells
• expressed on surface
• labelled as foreign cells

Question 14

What is cell therapy?

Answer 14

Delivery of cells to the patient to correct disease or damge
- may be combined with genetic strategies (secrete therapeutic protein, reprogramming immune cells)

Question 15

What is strimvelis? What does it treat?

Answer 15

First ex vivo stem cell gene therapy
- treats severe combined immunodeficiency cause by adenosine deaminase deficiency
- autologoes CD34+ cells expressing functional ADA
- (rare)

Question 16

How are cell therapies with CAR T cells done?

Answer 16

• 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

Question 17

What are approved CAR T cell therapies?

Answer 17

• kymriah
• yescarta
• tecartus
• breyanzi
• ABECMA
• carvykti

Question 18

What are emerging cell therapies?

Answer 18

• TCR-T cells
• CAR-M
• CAR-NK cells

Question 19

How do CAR T cells work?

Answer 19

• recognise antigen on tumour cell
• causes transcription of T cell effector function
  = perforin and granzyme release

Question 20

What was combination cell-gene therapy?

Answer 20

• 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)

Question 21

What are current approaches to nucleic acid therapy like?

Answer 21

Often transient
- varying degrees of success

Question 22

What is gene editing?

Answer 22

Permanently editing the genome to correct a defect, knocking down a specific gene/activating a gene

Question 23

What are ways of gene editing?

Answer 23

Break in double strand break
- gene disruption
- gene correction
- gene insertion

Question 24

What is an example of gene editing? What does it do?

Answer 24

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

Question 25

How could gene editing cure HIV?

Answer 25

Cause mutation in CCR5 expression
- prevents HIV from entering cells as not expressed on T cells

Question 26

What are examples of stem cell therapies?

Answer 26

• totipotent
• pluripotent
• multipotent

Question 27

What is stem cell therapy to cure blindness?

Answer 27

Limbal stem cell transplantation
- cure blindness due to corneal burning

Question 28

What does tissue engineering aim to do?

Answer 28

replace diseased or damaged livgin tissue with living tissue designed and contructed for the needs of each individual

Question 29

What are the steps in tissue engineering?

Answer 29

• isolate cells
• expand cell number
• seed on suitable scaffold
• culture under suitable conditions to generate a mature tissue
• implant tissue in patient

Question 30

What is a way of tissue engineering for implants?

Answer 30

3D bioprinting

Question 31

What is controlled drug delivery used for?

Answer 31

• long term treatment (entrap drug in polymer matrix, dif shapes and szes)
• small quantites released over a long period

Question 32

What are way of controlled drug delivery?

Answer 32

• polymer degrades over time, releasing drugs
• polymer doesnt degrade, drug slowly diffues
  (Microchips)

Question 33

Why would controlled drug delivery be favoured?

Answer 33

• sustained therapeutic plasma conc
• improved compliance - patient can’t forget dose

Question 34

What does targeted drug delivery aim to do?

Answer 34

• accumulate and retain drug at site of action
• minimise loss in transit
• protect drug from premature clearance
• aid intracellular delivery (in necessary)

Question 35

What are antibody-drug conjugates (ADCs)?

Answer 35

mAb therapy
- need to be combined with small drug chemotherapy/radiotherapy
- binds to specific targets, can deliver highly toxic drugs to site of action

Question 36

What are ADCs being developed for?

Answer 36

Delivery of chemotherapeutics to cancerous cells

Question 37

What are the current ADCs like on the market?

Answer 37

2 on the market, many nearing approval
- multiple drug molecules attaches via cleavable linker

Question 38

What is the Kadcyla ADC?

Answer 38

Combination os trastuzamab and cytotoxic drug
- increase median overall survival in HER2+ metastatic breast cancer by almost 6 months

Question 39

What are oncolytic viruses?

Answer 39

Viruses that break apart cancerous cells
- infect cancerous cells and cause lysis and apoptosis

Question 40

What does the enhanced permeability and retention have an effect on (EPR)?

Answer 40

• blood vessels in tumours are leaky
• macromolecules and nanoparticles easily enter, poorly drained
• accumulation in tumours is possible

Question 41

How could you use bacteria to fight cancer?

Answer 41

• oxygen deficient (hypoxic) areas, resistant to chemo/radiotherapy
• some are olbigate anaerobes, can colonise hypoxic areas

Question 42

What is an examples of a bacteria that could fight cancer?

Answer 42

Probiotic-guided CAR (ProCAR)-T cells