Gene Therapy Flashcards
What is gene therapy?
The introduction of genes into a person’s cells to replace or compensate for defective (mutant) genes that are responsible for a specific disease or medical problem.
The therapeutic (good) genes can be delivered by a customized vector such as a virus.
Using genetically engineered viruses to selectively kill cancer cells
How are genes delivered by viruses (safety & specificity)?
Modified viruses can be targeted to deliver genes to the correct population of cells. Tropism of virus must be altered (specificity)
In gene replacement, viruses are engineered so that they cannot replicate and destroy or harm cells of the patient. (safety)
Sometimes the patient may get sick and the patient may mount an immune response against the viral vector, preventing treatments from working. (safety)
What are the Hallmarks of a safe and effective gene therapy virus vector?
Targets the appropriate cells.
Transcribes and translates the correct gene product so that the gene product can function properly.
Causes NO toxic or harmful affects related to the gene delivery vehicle.
What are Two Ways to Deliver the Viral Vector to the Patient’s Cells?
In vivo therapy: the patient’s body is directly injected with the modified gene therapy vector.
Ex vivo therapy: the patient’s cells are removed, grown in culture dishes in the laboratory, incubated with the viral vector to introduce the genes, then transplanted back into the patient.
What are the applications of gene therapy?
- Gene replacement/augmentation
- Especially suited to single gene defects and discrete populations of target cells
- Oncolytic virotherapy
- Direct oncolysis
- efficient virus replication and lysis of tumor cells
- ONYX-15 specific lysis of p53-/- cells- Indirect oncolysis (Suicide/toxic genes) - Virotherapy + Immune stimulation To stimulate the host’s immune system, in particular to cancer cells
How does Oncolytic virotherapy use viruses to kill cancer cells?
Cancer therapy must first and foremost be safe with
few to no major side effects
Therapy must be highly specific for tumor cells
Therapy must be able to effectively kill tumor cells
Therapy must be able to “find” and destroy each
cancer cell in order to reduce the chance of recurrence
of the cancer
What are the Advantages of oncolytic virotherapy ?
1) Viruses can be engineered to be selective for cancer cells (targeted therapy)
2) Some oncolytic viruses, including the herpesviruses, have large genomes
that can be bio-engineered to augment the antitumor effect of the virus and increase safety
3) Some engineered viruses are selectively replication competent and thus can
efficiently spread throughout the tumor mass without destroying healthy tissue
4) Virotherapy can be combined with other therapeutic approaches such as:
- chemotherapy
- radiotherapy
- surgery
Overall idea is to kill the cancer cells
while sparing the healthy tissue
What are the types of oncolytic virotherapy?
Direct oncolysis
- direct killing of tumor cells by virus
- efficient targeting of cancer cells, virus replication, and lysis of tumor cells
Indirect oncolysis (Suicide/toxic genes) - viral delivery of suicide/toxic genes leading to cell death
Virotherapy combined with chemothearpy, radiotherapy,
or surgical resection
- find the right mix of anticancer agents that is most effective
Virotherapy + Immune stimulation or
- stimulate the host’s immune system to seek our and destroy cancer
- cancer vaccines
How does oncolytic virotherapy work?
the virus attaches to tumor cell surface antigens and is endocytosed
Replication of viral particles results in shutdown of normal tumor cells
Eventually enough viral particles are made to lyse the tumor cell
What is indirect killing (bystander effects)?
Gene therapy introduces viral gene into tumor cell
New gene transcribes/translates protein which interacts w/ externally administered compound like drugs or antibody-directed toxins which kill the tumor
