Gene Therapy for Wilson's Disease

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Questions and Answers

What is the application of adeno-associated viral vectors in gene delivery to muscle tissue?

Gene delivery to muscle tissue for treatment of muscle disorders.

What is the significance of codon bias in gene expression?

To fine-tune gene expression.

What is the purpose of designing a phase 2b trial of intracoronary administration of AAV1/SERCA2a in patients with advanced heart failure?

To evaluate the safety and efficacy of AAV1/SERCA2a gene therapy in patients with advanced heart failure.

How can AAV serotype 1 mediate more efficient gene transfer to pig myocardium compared to AAV serotype 2 and plasmid?

By increasing gene expression and improving gene transfer efficiency. Signup and view all the answers

What is the focus of massively parallel cis-regulatory analysis in the mammalian central nervous system?

To analyze cis-regulatory elements in the mammalian central nervous system. Signup and view all the answers

What is the application of gene therapy in treating Wilson's disease in a murine model?

To correct the genetic defect underlying Wilson's disease. Signup and view all the answers

How can codon engineering improve antibody expression in mammalian cells?

By optimizing codon usage for specific genes. Signup and view all the answers

What is the significance of tissue-specific codon usage in human genes?

To optimize gene expression in specific tissues. Signup and view all the answers

What is the major focus in pharmaceutical research and development in regard to gene delivery technologies?

The search for safe and effective gene delivery technologies. Signup and view all the answers

What is a driving factor for the search for alternative therapeutic platforms?

Limitations with current small molecule and protein therapeutic platforms. Signup and view all the answers

What type of license allows for noncommercial use, distribution, and reproduction of research in other areas?

Creative Commons Attribution-NonCommercial 4.0 International License. Signup and view all the answers

What is a challenge in gene expression targeting, especially in terms of accessibility?

Target accessibility. Signup and view all the answers

What is a potential application of gene delivery in therapeutic interventions, especially in terms of blood-brain barrier crossing?

Disease-state intervention. Signup and view all the answers

What is a significant consideration in promoter design for gene expression targeting?

Vector trafficking. Signup and view all the answers

What is a potential application of gene delivery in therapeutic interventions, especially in terms of liver-directed gene therapy?

Liver-directed gene therapy. Signup and view all the answers

What is a potential application of gene delivery in therapeutic interventions, especially in terms of vector trafficking and promoter design?

Production and clinical development of nanoparticles for gene delivery. Signup and view all the answers

What is the significance of the liver as a target tissue in AAV gene therapy, particularly in relation to systemic delivery?

The liver is readily accessible through systemic administration and can be efficiently transduced by many well-understood AAV variants, making it a suitable target for gene replacement therapies. Signup and view all the answers

What is the primary goal of gene therapy in monogenic, inherited diseases, and how is it achieved through AAV gene therapy?

The primary goal is gene replacement for defective genes, which is achieved by delivering a functional copy of the gene to the target tissue, using AAV vectors. Signup and view all the answers

What is the advantage of using skeletal muscle as a target tissue for AAV gene therapy, and how does it relate to the production of protein products?

Skeletal muscle has a low cellular turnover rate, allowing the transduced AAV gene product to be maintained for years, and serves as a production site for protein products that can act locally or systemically. Signup and view all the answers

What is the significance of the AAV1 vector in the context of gene therapy, and what is the approved gene therapy in Europe that utilizes this vector?

The AAV1 vector is efficient for gene transfer to skeletal muscle, and the approved gene therapy in Europe is Glybera, which uses AAV1 to encode the gene for lipoprotein lipase deficiency. Signup and view all the answers

What is the current stage of clinical trials for AAV gene therapies targeting the liver, and who are the sponsors of these trials?

The trials are currently in phase I/II, and are sponsored by academic groups, as well as biopharmaceutical companies such as Spark Therapeutics, Sangamo Therapeutics, UniQure, Dimension Therapeutics, and Biomarin. Signup and view all the answers

What is the potential advantage of using AAV gene therapy for gene expression targeting in the liver, and how does it relate to the treatment of hemophilia A and B?

The liver can be efficiently transduced by AAV vectors, allowing for targeted gene expression and potentially treating hemophilia A and B by replacing defective genes. Signup and view all the answers

What is the significance of vector trafficking in the context of AAV gene therapy, and how does it relate to the delivery of AAV vectors to target tissues?

Vector trafficking refers to the process by which AAV vectors are delivered to and interact with target tissues, and is a critical aspect of AAV gene therapy. Signup and view all the answers

What is the challenge of gene expression targeting in AAV gene therapy, and how does it relate to the design of promoters and gene expression cassettes?

The challenge is to design promoters and gene expression cassettes that enable targeted and regulated gene expression in specific tissues, while minimizing off-target effects. Signup and view all the answers

Study Notes

Gene Therapy and AAV Vectors

AAV (Adeno-associated virus) vectors have been used for gene therapy in clinical trials, with potential applications in treating monogenic diseases.
Systemic administration of AAV vectors has been used to target the liver, with ongoing trials for hemophilia A and B, and other inherited diseases.
The liver is a readily accessible tissue through systemic administration and is easily transduced by many AAV variants.
Intramuscular delivery is another common strategy, with the only approved AAV gene therapy in Europe being Glybera, which encodes the gene for lipoprotein lipase deficiency.

AAV Vector Characteristics

AAV vectors have a unique biology and are simple to construct.
AAV vectors have been used for gene delivery to muscle tissue, with the potential to efficiently transduce skeletal muscle.
Muscle cells serve as a production site for protein products that can act locally or systemically.
The transduced AAV gene product is maintained in muscle cells as an episome for years, as shown in non-human primate studies.

Gene Therapy Development

The search for safe and effective gene delivery technologies has been a major focus in pharmaceutical research and development.
Gene therapies have the potential to accommodate limitations of current small molecule and protein therapeutic platforms.
The development of AAV vectors has been driven by the need for alternative therapeutic platforms that can target inaccessible tissues.

Clinical Trials

Several clinical trials are ongoing for AAV gene therapy, sponsored by academic groups and biopharmaceutical companies such as Spark Therapeutics, Sangamo Therapeutics, UniQure, Dimension Therapeutics, and Biomarin.
Trials are currently in phase I/II, with the goal of gene replacement for defective genes in monogenic diseases.

References

The text cites multiple references, including studies on AAV vectors, gene therapy, and muscle tissue transduction.

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Description

This quiz is about gene therapy as a potential treatment for Wilson's disease, a genetic disorder affecting copper metabolism. It covers research on gene delivery to muscle tissue and cis-regulatory analysis in mammals.