L30 - New & Emerging Drug Technologies Flashcards

1
Q

What does a mutation in DNA result in?

A

Defective protein requires for normal cell function
= causes disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What are some diseases are exacerbated by?

A

Increased levels of particular proteins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

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

A

Delivering exogenous protein

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What can nucleic acids be used as?

A

Treatment in all scenearios

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What does therapeutic protein overcome?

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is siRNA? What does it do?

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What are advantages of siRNA?

A
  • readily designed
  • readily synthesised
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is miRNA? What is it derived from?

A

Micro RNA
- genes that specifically code miRNAs (not proteins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What are miRNA important in?

A

Regulating gene expression (1/3 of genes)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What are advantages of miRNA?

A
  • dont cause mRNA destructions (repress or destabilise)
  • strong evidence of involvement in diseases states (inc. cancer)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What can be delivered to cells to replace missing miRNAs?

A

DNA coding underexpressed or missing miRNAs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What can overexpressed miRNAs be inhibited by?

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What are RNA vaccines?

A
  • viral mRNA absorbed by cells
  • expressed on surface
  • labelled as foreign cells
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is cell therapy?

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is strimvelis? What does it treat?

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

How are cell therapies with CAR T cells done?

A
  • 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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What are approved CAR T cell therapies?

A
  • kymriah
  • yescarta
  • tecartus
  • breyanzi
  • ABECMA
  • carvykti
18
Q

What are emerging cell therapies?

A
  • TCR-T cells
  • CAR-M
  • CAR-NK cells
19
Q

How do CAR T cells work?

A
  • recognise antigen on tumour cell
  • causes transcription of T cell effector function
    = perforin and granzyme release
20
Q

What was combination cell-gene therapy?

A
  • 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)
21
Q

What are current approaches to nucleic acid therapy like?

A

Often transient
- varying degrees of success

22
Q

What is gene editing?

A

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

23
Q

What are ways of gene editing?

A

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

24
Q

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

A

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

25
How could gene editing cure HIV?
Cause mutation in CCR5 expression - prevents HIV from entering cells as not expressed on T cells
26
What are examples of stem cell therapies?
- totipotent - pluripotent - multipotent
27
What is stem cell therapy to cure blindness?
Limbal stem cell transplantation - cure blindness due to corneal burning
28
What does tissue engineering aim to do?
replace diseased or damaged livgin tissue with living tissue designed and contructed for the needs of each individual
29
What are the steps in tissue engineering?
- isolate cells - expand cell number - seed on suitable scaffold - culture under suitable conditions to generate a mature tissue - implant tissue in patient
30
What is a way of tissue engineering for implants?
3D bioprinting
31
What is controlled drug delivery used for?
- long term treatment (entrap drug in polymer matrix, dif shapes and szes) - small quantites released over a long period
32
What are way of controlled drug delivery?
- polymer degrades over time, releasing drugs - polymer doesnt degrade, drug slowly diffues (Microchips)
33
Why would controlled drug delivery be favoured?
- sustained therapeutic plasma conc - improved compliance - patient can’t forget dose
34
What does targeted drug delivery aim to do?
- accumulate and retain drug at site of action - minimise loss in transit - protect drug from premature clearance - aid intracellular delivery (in necessary)
35
What are antibody-drug conjugates (ADCs)?
mAb therapy - need to be combined with small drug chemotherapy/radiotherapy - binds to specific targets, can deliver highly toxic drugs to site of action
36
What are ADCs being developed for?
Delivery of chemotherapeutics to cancerous cells
37
What are the current ADCs like on the market?
2 on the market, many nearing approval - multiple drug molecules attaches via cleavable linker
38
What is the Kadcyla ADC?
Combination os trastuzamab and cytotoxic drug - increase median overall survival in HER2+ metastatic breast cancer by almost 6 months
39
What are oncolytic viruses?
Viruses that break apart cancerous cells - infect cancerous cells and cause lysis and apoptosis
40
What does the enhanced permeability and retention have an effect on (EPR)?
- blood vessels in tumours are leaky - macromolecules and nanoparticles easily enter, poorly drained - accumulation in tumours is possible
41
How could you use bacteria to fight cancer?
- oxygen deficient (hypoxic) areas, resistant to chemo/radiotherapy - some are olbigate anaerobes, can colonise hypoxic areas
42
What is an examples of a bacteria that could fight cancer?
Probiotic-guided CAR (ProCAR)-T cells