TD: Gene Therapy 2

Question 1

What are potential targets for gene therapy?

Answer 1

So far all approved at somatic (not germline) - culture of cells taken from patient and grown up in lab, treated using gene protocol and then transferred back into body

Question 2

Describe gene therapy and CF

Answer 2

The thick secretion enviroment is a good enviroment for bacteria.

Mutation at position 508 (phenylalanine) in the codon of AA for protein

• Progress?
• In 1990
  
  • delivery of normal CFTR gene to cells in culture
    
    • correction of faulty gene
• Human studies
  
  • Gene transfer
    
    • Probably too small to show therapeutic benefit
    • Lasted only a few days

Question 3

Problem and solution to gene therapy for CF

Answer 3

Question 4

Describe gene therapy and CVD

Answer 4

Adv gene therapy:- longer lasting effects, less hospitalisation, less medication

Angiongenesis - improving/restoring blood flow to tissues which have lost blood by synthesising and enhacing growth of new blood vessels

Question 5

Peripheral aterial disease and gene therapy

Answer 5

Question 6

Cancer and gene therapy

Answer 6

P53 - guardian of the genome - monitors cell replication and can slow down

Deliveer healthy copies of P53 is one method

Another method is SATIR - targets cancer cells but not healthy

Question 7

Gene therapy and RA

Answer 7

Question 8

Antisense therapy

Answer 8

Question 9

What potential diseases/ conditions could antisense drugs be used for?

What is an example already?

Answer 9

Question 10

Describe the mechanism of antisense drugs

Answer 10

Question 11

What are the ethical dilemas associated with gene therapy?

Answer 11

• Altering the body’s set of basic instructions
• Who decides what constitutes ‘abnormal’
• Financial
  
  • Only available to the wealthy
• Sociological
  
  • Less accepting of disorder
• Artificial enhancement
  
  • Intelligence, athleticism
• “Designer babies”
  
  • Inheritance of fatal genes could be prevented
  • but, so could other harmless traits
• Germline therapy
  
  • Gene would be inherited
  • Unexpected long term side effects
    
    • Foetal developmen
    • Unborn individual has no choice

Question 12

Problems with gene therpy

Answer 12

• Longevity of effect
  
  • Therapeutic DNA needs to be long lived and stable
  • Multiple rounds of gene therapy
• Immune response
  
  • Stimulation in response to foreign gene
  • Difficult for gene therapy to be repeated in a patient
  • Fear that viral vector may become reactivated
• Multigene disorders
  
  • Combined effects of variations in genes
  • Heart disease, diabetes, Alzheimer’s
• Tumour formation
  
  • DNA integrated in wrong place in the genome
  • X-linked severe combined immunodeficiency (X-SCID) patients
    
    • hematopoietic stem cells were transduced with a corrective transgene
    • Retrovirus
    • Development of T cell leukaemia in 3 of 20 patients.