week 13 to 14 p1

• Gene therapy


  An experimental technique that uses genes to treat or prevent disease by correcting the underlying genetic problem

  
• Stem cell therapy


  A medical approach that treats or prevents disease by correcting the underlying genetic problem
• DNA replication mistakes


  Mistakes that can occasionally occur when a DNA polymerase inserts a wrong base, which can lead to serious consequences such as cancer
• Scientists began to investigate gene therapy

  1980s

  
• The director of the NIH approved the first clinical protocol to insert a foreign gene into the immune cells of persons with cancer

  January 19, 1989

  
• The first approved gene therapy procedure was performed on a four-year-old girl born with severe combined immunodeficiency (SCID)


  September 14, 1990

  
• Despite the viral horror stories written by the popular media, the initial trial was largely a success, and the most recent report on this individual in 2004 noted that she is thriving as an 18-year-old teenager
• Over the next ten years, 300 clinical gene therapy trials were performed on about 3000 individuals

  
• The field was then blackened with the death of an 18-year-old male four days after the introduction of 38 trillion particles of recombinant adenovirus into his liver
• Despite this tragedy, researchers continue to move forward because of the great promise of novel genetic treatments that, when perfected, will likely outshine current methods, such as protein therapy or pharmacotherapeutics, for treatment of many diseases and defects

  
• Types of Gene Therapy

  • Somatic cell gene therapy
  • Germline gene therapy
• Somatic cell gene therapy

  The transfer of a section of DNA to any cell of the body that doesn't produce sperm or eggs, where the new DNA doesn't enter the eggs or sperm and affects only the individual patient

  
• Germline gene therapy


  The transfer of a section of DNA to cells that produce eggs or sperm, which involves the modification of germ cells (gametes) that will pass the change on to the next generation

  
• Countries prohibiting the application of germline gene therapy in human beings: Australia, Canada, Germany, Israel, Netherlands, Switzerland
• Approaches of Gene Therapy

  • Ex vivo
  • In vivo

  
• Ex vivo gene therapy

  The transfer of genes in cultured cells that will be reinjected into the body of the patient

  
• In vivo gene therapy

  The introduction of the therapeutic gene directly into the body, which can be carried out using viral or non-viral vectors

  
• Ex vivo gene therapy

  1. Isolate cells with genetic defect from patient

  2. Grow these cells in culture

  3. Introduce therapeutic gene into cultured cells using a vector

  4. Reintroduce genetically altered target cells into patient's body

  
• Types of vectors


  • Viral vectors
  • Non-viral vectors
• Viral vectors


  Recombinant viruses used to deliver the therapeutic gene, including retroviruses, adenoviruses, adeno-associated viruses, and herpes simplex viruses

  
• Non-viral vectors


  Carriers for the therapeutic gene that are not viruses, including naked DNA, chemically enhanced delivery, and physically enhanced delivery

  
• Viral vectors have been utilized in a number of gene therapies due to the virus' natural ability to access the cells of the body

  
• Non-viral vectors are currently being evaluated for long-term expression of the therapeutic genetic material

  
• Types of viral vectors

  • Retroviruses
  • Adenoviruses
  • Adeno-associated viruses
  • Herpes simplex viruses
• Retroviruses


  Viruses that insert a copy of their RNA genome into the DNA of a host cell, changing the genome of that cell

  
• Adenoviruses


  Common viruses that infect the lining of the eyes, airways, lungs, intestines, urinary tract, and nervous system, causing fever, coughs, sore throats, diarrhea, and pink eye

  
• Adeno-associated viruses


  Small viruses that insert genetic material at a specific point on chromosome 19, causing no known disease and triggering a very low immune response
• Herpes simplex viruses


  Double-stranded DNA viruses that infect neurons and can be transmitted from person to person through direct contact
• For COVID-19 viral vector vaccines, the vector (not the virus that causes COVID-19, but a different, harmless virus) will enter a cell in our body and then use the cell's machinery to produce a harmless piece of the virus that causes COVID-19, triggering an immune response

  
• Other vectors used in COVID-19 vaccines

  • Using DNA
  • Using mRNA
  • Using inactivated virus (traditional vaccine)
• Non-viral vectors


  Carriers for the therapeutic gene that are not viruses, including direct introduction of DNA, creation of artificial lipid spheres, and chemical linking of DNA to molecules

  
• The FDA has not approved any human gene therapy product for sale due to safety concerns, including a death in 1999 and children developing leukemia-like conditions in 2003
• Gene therapy can be done in either somatic or germline cells, but there are no clinical trials on human germline gene therapy due to safety and ethical concerns

  
• Gene therapy effectively treats several diseases due to increased understanding of disease pathogenesis and improved gene delivery technologies

  
• Issues with gene therapy

  • Short-lived effects
  • Immune response
  • Viral vector issues
  • Difficulty treating multigene disorders
• In 2018, He Jiankui and his team used CRISPR-Cas9 to edit the genes of twin girls as embryos, resulting in the birth of the world's first genetically modified babies
• In 2021, China made human germline editing for clinical use a crime and introduced new measures to strengthen existing guidelines and rules on life sciences and medical research involving humans