5.+Medical+Gene+Therapy

=Gene Therapy in Medicine=

Gene therapy has the potential to fix single cell genetic disorders. There are 4,200 known or suspected single cell gene disorders that have been reported to exist affecting about 1% of the human population. (e.g. cystic fibrosis, hemophilia, muscular dystrophy, or sickle cell anemia)

Goal: Insert healthy copy of gene, into a malfunctioning cell, without harming the cell's healthy genes to enable the cell to function properly.

Different methods of delivery:


 * Retrovirus:** Retroviruses contain about ten genes. The normal function of a retrovirus is to insert it's genetic material into the target cells genome to alter it permanelty. Scientist remove the virus' genetic material and replace it with the genetic material they wish to deliver to the defective cells. After disabling the portion of the virus that forces a cell to replicate it's gentic material, they introduce the virus to the body in question.
 * Pros of this type of gene therapy: Retro viruses target very specific cells. (e.g. rabies virus targets the nerve cells in the brain while common cold virus targets the tissues lining the nose)
 * Cons of this type of gene therapy: Inserting new genes into a cells genome may cause mutations or disrupt a cell linked to cancer there by causing cancer to develop.


 * Adenovirus**: Like retrovirus, uses host cell to replicate. Unlike retrovirus does not insert DNA into host cell's genome.
 * Pros: No risk of mutation of cells, or disruption of genome sequences.
 * Cons: Can trigger immune response from the body causing the body to kill off the altered cells rendering the therapy useless. Along with that if the body has already naturally come into contact with an adenovirus it could have antibodies already formed against the virus iniating an immune response.

Nose sprays have been developed to deliver liposomes directly to the lungs of cystic fibrosis patients.
 * Liposome gene therapy**: This method of delivery uses a fatty cell, liposome, to carry healty human genes into target cell. First the health gene is injected into a plasmid, which is the tiny ring of DNA that replicates in bacteria. Then the plasmid gets a covering of liposomes. The plasmid will then fuse with the liposome droplets creating a tunnel for the healthy genes to enter cells.
 * Pros: Safer then modified viruses.
 * Cons: requires a very large number of infected liposomes to have desired effect. Has to be directly introduced to infected cells.


 * Issues and Advancements in Gene Therapy (Vectors)**
 * Three types of vectors will be discussed:
 * INDENT: Retrovirus vectors
 * INDENT: HIV is a retrovirus.
 * INDENT: Adenovirus vectors
 * INDENT: Known for causing upper respiratory tract infections.
 * INDENT: Liposome vectors
 * INDENT: Imagine a liposome as being similar to a soap bubble.


 * Retrovirus Vectors**
 * The normal function of a retrovirus is to insert it's genetic material into the target cells genome to alter it permanelty.
 * Scientists remove the viruses genetic material and replace it with the genetic material they wish to deliver to the defective cells.
 * Inactivation of the virus leads to its use in gene therapy.
 * Pros: Retroviruses target very specific cells depending on the type of virus.
 * Cons: Inserting new genes into a cells genome may cause mutations or disrupt a cell linked to cancer thereby causing cancer to develop


 * Adenovirus Vectors**
 * Like retrovirus, uses host cell to replicate.
 * Unlike retrovirus does not insert DNA into host cell's genome.
 * Pros: No risk of mutation of cells, or disruption of genome sequences.
 * Cons: Can trigger immune response from the body causing the body to kill off the altered cells rendering the therapy useless.
 * INDENT: In addition, if the body has already naturally come into contact with an adenovirus it could have antibodies already formed against the virus iniating an immune response.


 * Liposome Vectors**
 * Uses a fatty cell, a liposome, to carry healty human genes into target cell.
 * The gene to be delivered is "transformed" into a small circular ring of DNA (a plasmid), and is then inserted into a liposome.
 * Pros: Safer then modified viruses.
 * Cons: requires a very large number of infected liposomes to have desired effect. Has to be directly introduced to infected cells.
 * Nose sprays have been developed to deliver liposomes directly to the lungs of cystic fibrosis patients.




 * REFERENCE: Lavorini-Doyle C, Gebremedhin S, Konopka K, Düzgüneş N. 2009. Gene delivery to oral cancer cells by nonviral vectors: why some cells are resistant to transfection. //J Calif Dent Assoc,// 37(12):855-8.

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