gene therapy

• Gene therapy


  Using various mechanisms to alter a person's genetic material to treat, or cure, diseases
• Gene therapy


  • As scientists gain a better understanding of the human genome, the possibilities of gene therapy being able to replace a faulty gene, inactivate a faulty gene or insert a new gene are growing
• Genetic diseases being treated/researched with experimental gene therapy techniques

  • Severe combined immunodeficiency (SCID)
  • Leber congenital amaurosis
  • β-thalassaemia
  • haemophilia B
• Most gene therapies are still in the clinical trial stage because scientists are having difficulty finding delivery systems that can transfer normal alleles into a person's cells and how to ensure the gene is correctly expressed once there
• Vectors


  Delivery systems used for gene therapy
• Vectors used for gene therapy

  • Viruses (eg. retroviruses and lentiviruses)
  • Non-viral vectors (eg. liposomes and 'naked' DNA)
• Somatic gene therapy


  • Changes in genetic material are targeted to specific cells and so will not be inherited by future generations
  • Often the effects of changing the somatic cells are short-lived
• Ex vivo somatic gene therapy

  1. The new gene is inserted via a virus vector into the cell outside the body

  2. Blood or bone marrow cells are extracted and exposed to the virus which inserts the gene into these cells

  3. These cells are then grown in the laboratory and returned to the person by an injection into a vein
• In vivo somatic gene therapy

  The new gene is inserted via a vector into cells inside the body
• Inserting new genetic material into germ cells (cells involved in sexual reproduction eg. gametes or an early embryo) is illegal in humans as any changes made to the genetic material of these cells is potentially permanent and could therefore be inherited by future generations
• Severe combined immunodeficiency (SCID)

  Caused by the body's inability to produce adenosine deaminase (ADA), an enzyme that is key to the functioning of the immune system
• Treating SCID with ex vivo somatic gene therapy

  1. A virus transfers a normal allele for ADA into T-lymphocytes removed from the patient

  2. The cells are then returned via an injection

  3. This is not a permanent cure as the T-lymphocytes are replaced by the body over time and therefore the patient requires regular transfusions every three to five months to keep their immune systems functioning
• Vectors used for SCID treatment

  • Originally retroviruses were used, however these viruses insert their genes randomly into a host's genome which means they could insert the gene into another gene or into a regulatory sequence of a gene (which could result in cancer)
  • Researchers switched to using lentiviruses or adeno-associated viruses as vectors
  • Lentiviruses also randomly insert their genes into the host genome however they can be modified to not replicate, whereas adeno-associated viruses do not insert their genes into the host genome and therefore the genes are not passed onto the daughter cells when a cell divides
• Leber Congenital Amaurosis


  An inherited eye disease that causes blindness due to damage to the light receptors in the retina
• Treating Leber Congenital Amaurosis with in vivo somatic gene therapy

  1. Doctors injected adeno-associated viruses that contained the normal alleles of one of the genes that caused damage to the photoreceptors into the retina

  2. All patients that have had the injections have shown improvement in their eyesight
• Gene therapy in somatic cells is not permanent, whereas in germ cells it is