Download - Gene Therapy: Molecular Bandage? An Overview of the curriculum module available on Learn.Genetics
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Gene Therapy: Gene Therapy: Molecular Bandage?Molecular Bandage?
An Overview of the curriculum module available on
Learn.Genetics
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What is gene therapy?
• A way to treat diseases caused by mutated genes
• Adding a normally functioning copy of the gene(s) to enough affected cells to restore normal function.
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Which disorders are candidates for gene therapy treatment?
• Disorders due to mutations in one or more genes– Single-gene disorders are more easily treated
• The responsible gene is known– Copies have been made in the laboratory– The role of the protein encoded by the gene is known– Adding a normal gene will fix the problem
• The affected tissues are known and accessible
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Hallmarks of Successful Gene Therapy• Targeting the right cells
– Ensuring that the gene gets to the affected cells
• Activating the gene– The gene must get into the cells’ nuclei– The gene must be “turned on”; i.e., transcription
and translation must take place at the correct time
• Integrating the gene into the cells– DNA is integrated into the cells’ chromosomes or
otherwise survives in the nucleus
• Avoiding harmful side effects– The gene delivery vehicle must not trigger an
immune response
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How do you do gene therapy?
• Identify the gene responsible for the disorder• Make copies of the normal gene• Insert the copies into vectors (such as viruses)
– Remove the viral DNA– Insert the gene of interest
• “Infect” the affected cells with the vector– The normal gene is carried into the nucleus– The DNA may integrate into the genome
• Activate the gene– Transcription and translation takes place
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Critical factors in choosing a vector• Gene size
– Most vectors have an upper limit on the number of base pairs they can hold
• Target tissue– Some vectors only infect a particular type of cell– Other vectors can be engineered to infect a particular
type of cell
• Integration into the genome– Vectors that do not lead to genome integration have a
short-lived effect– Vectors that integrate into the genome or are copied
along with the genome have a long-lasting effect– Vectors that lead to random integration may disrupt
other genes leading to negative side-effects
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Ways to Deliver Genes
• In Vivo– Inject the vector directly into the desired cells in the
body
• Ex Vivo– Isolate the desired cells from the body– Culture the cells in a Petri dish in the laboratory– Deliver the genes to the cells using a vector– Activate the genes and make sure they have
integrated properly– Return the modified cells to the body
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Challenges in Gene Therapy• Gene delivery and activation
– Genes must be delivered to a large number of cells (several million) of the affected tissue
– The genes must be activated for transcription and translation to take place
• Introducing changes into the germline– Not causing changes in sperm or eggs, if this is not
desired
• Triggering an immune response– Can be fatal
• Disrupting genes in the target cells– Can cause other diseases or problems
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Gene Therapy Successes & Failures
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Ethical and Social Issues
• Patient safety while participating in clinical trials
• Which applications are therapies and which are enhancements?– “Designer” babies
• Effects on future generations if germline cells are allowed to be altered
• Access to gene therapies
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Gene Therapy Module on Learn.Genetics:
Tools of the Trade
Space Doctor
Cystic Fibrosis Case Study
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Vector Selector
• You are a researcher at Advanced Bio Delivery Systems
– Supplies gene therapy vectors
• Marketing department requests your assistance– Want to sell ABDS vectors to biotech companies
pursuing specific gene therapies
• Your job:– Research disorders these companies are targeting– Decide on the vector that you think will work the best
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Vector SelectorKey issues in deciding which vector to select:• Size of the gene
– Will the replacement gene fit into the vector?
• Tissue type– Does the vector naturally target, or can it be
engineered to target, the appropriate type of cells?
• Cell cycle stage (dividing vs. non-dividing)– Are the cells at the right stage of the cell cycle for
the vector to “infect” them?
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Vector Selector• Read the situation assigned to your group• Decide on the best vector to use for that
disease– Use the Vector Types Table as a reference to
assist in making your decision
• Select a reporter who will report:– The disease– The vector you selected– The reasons why you thought this was the best
vector for the job
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