Course: SAT 170 Introductory Biotechnology

Unit 11 Reading and Multimedia Assignment

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- Unit 11
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- Unit 11 Key Terms (Selected)

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“Overview of Gene Therapy” by Boundless, CC BY SA 3.0

https://www.boundless.com/biology/biotechnology/biotechnology-and-everyday-life/overview-gene-therapy/

Reading Assignment: Overview of Gene Therapy
In gene therapy, a normal copy of a gene mutated in a patient is inserted into that patient's genome, replacing the mutated allele.

Human SCID (Severe Combined Immunodeficiency) is a prenatal disorder of T lymphocyte development that depends on the expression of numerous genes. The knowledge of the genetic basis of SCID is essential for diagnosis and treatment. About 25% of SCID cases are the result of the child being homozygous for a defective gene encoding the enzyme adenosine deaminase (ADA). The normal catabolism of purines is deficient, and this is particularly toxic for T cells and B cells.

To perform gene therapy for a particular disease, the gene causing the disease must be identified and cloned. This has been done for the ADA gene. It must then be inserted in cells that can take up long-term residence in the patient. So far, this means removing the patient's own cells, treating them in tissue culture, and then returning them to the patient. It must be inserted in the DNA so that it will be expressed adequately; that is, transcribed and translated with sufficient efficiency that worthwhile amounts of the enzyme are produced.

All of these requirements seem to have been met for SCID therapy using a retrovirus as the gene vector. Retroviruses have several advantages for introducing genes into human cells. First, their envelope protein (env) enables the virus to infect human cells. RNA copies of the human ADA gene can be then incorporated into the retroviral genome using a packaging cell. The packaging cell produces a crop of retroviruses with the envelope protein needed to infect the human target cells, an RNA copy of the human ADA gene, reverse transcriptase (needed to make a DNA copy of the ADA gene that can be inserted into the DNA of the target cell), and none of the genes that would enable the virus to replicate in its new host. Once the virus has infected the target cells, this RNA is reverse transcribed into DNA and inserted into the chromosomal DNA of the host.

The biology of human gene therapy remains complex and many techniques need further development. Many diseases and their strict genetic link need to be understood more fully before gene therapy can be used appropriately. The public policy debate surrounding the possible use of genetically engineered material in human subjects has been equally complex. Major participants in the debate have come from the fields of biology, government, law, medicine, philosophy, politics, and religion, each bringing different views to the discussion.

Some of the potential problems include the short-lived nature of gene therapy. Before gene therapy can become a permanent cure for any condition, the therapeutic DNA introduced into target cells must remain functional and the cells containing the therapeutic DNA must be long-lived and stable. Another issue is the body's immune response – any time a foreign object is introduced into human tissues, the immune system has evolved to attack the invader. The risk of stimulating the immune system in a way that reduces gene therapy effectiveness is always a possibility. Viruses, the carrier of choice in most gene therapy studies, present a variety of potential problems to the patient — toxicity, immune and inflammatory responses, and gene control and targeting issues. In addition, there is always the fear that the viral vector, once inside the patient, may recover its ability to cause disease.