Virology and Gene Therapy

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Questions and Answers

What is the main idea behind oncolytic gene therapy?

To introduce tumor-suppressor genes to prevent uncontrolled cellular growth

To directly induce tumor cell lysis through viruses (correct)

To deliver proapoptotic genes to target cancer cells

To stimulate or enhance antitumor immunity

What is the advantage of using HSV as a viral vector in oncolytic gene therapy?

It can integrate into the host genome, ensuring long-term expression

It is not specific to tumor cells, allowing for broader targeting

It is highly immunogenic, stimulating a strong immune response

It maintains its genome as an episomal element, reducing the risk of insertional mutagenesis (correct)

What is the purpose of tumor-suppressor gene therapy?

To prevent uncontrolled cellular growth by introducing tumor-suppressor genes (correct)

To stimulate or enhance antitumor immunity

To introduce a gene that will induce tumor cell lysis

To deliver proapoptotic genes to target cancer cells

What is the characteristic of Vaccinia virus that makes it attractive for oncolytic gene therapy?

It has a rapid and efficient cycle Signup and view all the answers

What is a characteristic of the vaccinia virus?

It inhibits host protein synthesis Signup and view all the answers

What is the indirect form of suicide gene therapy?

Using an enzyme-activated prodrug that will be converted into a lethal drug in cells Signup and view all the answers

What is the purpose of the herpes simplex virus thymidine kinase gene (HSV-tk) in suicide gene therapy?

To convert ganciclovir into a monophosphate Signup and view all the answers

What is the main idea behind immunomodulatory gene therapy?

To stimulate or enhance antitumor immunity Signup and view all the answers

What is the advantage of HSV as a viral vector for targeting the central nervous system?

It has a natural tropism to neurons Signup and view all the answers

What is the mechanism of action of Imlygic?

It stimulates the patient’s immune system to destroy cancer cells Signup and view all the answers

What type of gene therapy is Gendicine used for?

Tumor-suppressor gene therapy Signup and view all the answers

What is the characteristic of HSV replication-competent vectors?

They can replicate only in tumor or dividing cells Signup and view all the answers

What is the role of proinflammatory genes in immunomodulatory gene therapy?

To stimulate the patient’s immune system Signup and view all the answers

What is the purpose of the cytochrome P450 system in suicide gene therapy?

To convert a prodrug into a toxic compound Signup and view all the answers

What is the advantage of using vaccinia virus in cancer immunotherapy applications?

It elicits strong immune responses Signup and view all the answers

What is the ultimate goal of oncolytic gene therapy?

To kill cancer cells Signup and view all the answers

What is CAVTAK, as mentioned in the text?

An oncolytic coxsackievirus Signup and view all the answers

What is the main characteristic of neurodegenerative diseases?

Slow, progressive, and irreversible loss of neurons Signup and view all the answers

What is the primary goal of gene therapy strategies for Alzheimer's disease?

To improve AD-associated deficits Signup and view all the answers

Which gene therapy approach involves the use of a viral vector to deliver a gene that produces the enzyme glutamic acid decarboxylase (GAD) to the brain?

Parkinson's disease treatment Signup and view all the answers

What is the role of tumor-suppressor genes in cancer treatment?

To inhibit cancer cell growth Signup and view all the answers

What is the result of combining an immunological checkpoint blockade with oncolytic gene therapy in a phase Ib clinical trial for advanced melanoma?

Very good response and disease control rates Signup and view all the answers

Which of the following is an example of oncolytic gene therapy?

Combination of an immunological checkpoint blockade with CAVTAK Signup and view all the answers

What is the main characteristic of Alzheimer's disease?

Accumulation of abnormal protein deposits in the brain Signup and view all the answers

Study Notes

Gene Therapy for Cancer

Suicide gene therapy can be achieved through two strategies: indirect form using an enzyme-activated prodrug, and direct form using proapoptotic genes.
Oncolytic gene therapy involves applying viruses directly into the tumor to induce tumor cell lysis.
Immunomodulatory gene therapy introduces a gene to stimulate or enhance antitumor immunity.
Tumor-suppressor gene therapy introduces tumor-suppressor genes to prevent uncontrolled cellular growth.

Viral Vectors for Oncolytic Gene Therapy

Herpes Simplex Virus (HSV) is attractive as a vector due to its natural tropism to neurons, and ability to replicate only in tumor or dividing cells.
HSV maintains its genome as an episomal element, reducing the risk of insertional mutagenesis.
Vaccinia virus is attractive as a vector due to its rapid and efficient cycle, ability to shut down host cell functions, and induce strong immune responses.

Suicide Gene Therapy

The herpes simplex virus thymidine kinase gene (HSV-tk) converts the antiviral drug ganciclovir (GCV) to monophosphate, leading to cell death.
Other systems employ the cytochrome P450 and the prodrugs cyclophosphamide (CPA).

Oncolytic Gene Therapy

Imlygic is a gene therapy that uses a weakened form of herpes simplex virus type 1 to infect and multiply inside melanoma cells, killing them.
Imlygic also makes the infected cells produce the human cytokine granulocyte macrophage colony stimulating factor gene, which stimulates the patient's immune system to destroy cancer cells.

Immunomodulatory Gene Therapy

This strategy can take advantage of the enhancement of the immune response through the delivery of proinflammatory genes.
The combination of an immunological checkpoint blockade with CAVTAK led to a good response and disease control rates in a phase Ib clinical trial for advanced melanoma.

Tumor-Suppressor Gene Therapy

Gendicine is a gene therapy medication used to treat patients with squamous cell carcinoma linked to mutations in the P53 gene.

Candidate Conditions for Gene Therapy

Neurodegenerative diseases include Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and others.

Alzheimer's Disease

Alzheimer's disease is the most common neurodegenerative disorder worldwide, characterized by impairments in memory and behavior.
The disease is characterized by the accumulation of abnormal protein deposits in the brain, particularly beta-amyloid plaques and tau tangles.
Gene therapy strategies have been tested in preclinical studies, focusing on the expression of neurotrophic factors, especially the nerve growth factor (NGF).

Parkinson's Disease

Parkinson's disease is a progressive neurodegenerative disorder that affects movement, coordination, and balance.
It is caused by the degeneration of dopamine-producing neurons in the brain and the formation of intracellular inclusions of α-synuclein.
A viral vector delivering a gene that produces the enzyme glutamic acid decarboxylase (GAD) to the brain enhanced disease symptoms.

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Description

Explore the unique features of vaccinia virus, its applications in cancer immunotherapy, and the principles of suicide gene therapy using the herpes simplex virus thymidine kinase gene.