Gene Therapy Flashcards
What is gene therapy?
Additional or alteration of genes to treat disease?
What is the difference between somatic cell and germline gene therapies?
Somatic cell gene therapy treats a disorder while germline gene therapy prevents disease. Germline gene therapy is not considered safe and is prohibited in the USA
What factors should be taken into consideration when designing a gene therapy protocol?
Specificity, efficiency, age of disease, immunogenicity of vector, potential for insertional mutagenesis, magnitude and duration of response, manufacturing
What cells are generally considered the best gene therapy targets? Why?
Bone marrow stem cells/hematopoietic stem cells - they are accessible, have a long lifespan, and proliferate
How does in vivo gene therapy differ from ex vivo gene therapy?
In vivo gene therapy requires delivery of the gene therapy into cells in the body. Ex vivo involves removing cells from the boxy, inserting the gene therapy, and then replacing the cells in the body
What are characteristics of an ideal delivery vector?
Targets specific cells, efficient gene transfer, targets both dividing and non-dividing cells, longterm gene expression, safe repeat dosing, accommodates large genes, easy and inexpensive to produce
Adenoviruses are common gene therapy vectors. What are some of the advantages and disadvantages?
Advantages - transduce non-dividing cells, accepts large genes, no possibility of insertional mutagenesis
Disadvantages - not targetted to specific cells, does not integrate into genome and requires repeat dosing, elicits immune response, pre-existing host antibodies
What are Adeno-associated viruses? What are some of the advantages and disadvantages?
Parvovirus that requires an adenovirus for replication
Advantages - Transduces non-dividing cells, less risk of immune response, effects lasting months to years
Disadvantages - Does not integrate into genome, small genes only
What are the advantages and disadvantages of retroviruses as viral vectors for gene therapy?
Advantages - integrate into host genome, do not trigger immune response, moderate gene size
Disadvantages - Only transduces dividing cells, possibility of insertional mutagenesis
How do Lentiviruses differ from Retroviruses as viral vectors?
Lentiviruses are retroviruses and transduce non-dividing cells. They stably integrate into the genome and pose less risk of insertional mutations.
What non-viral methods are used for gene therapy?
Polymers, lipids, peptides, inorganic materials, hybrid systems
Non-viral vectors, such as naked DNA and liposome-DNA, are considered safer for gene therapy. What are some advantages and disadvantages of use?
Advantages - Safe, easy production, no gene limit, low immunogenicity
Disadvantages - Low efficiency, transient expression, hard to target
Liposome-DNA is slightly more efficient than naked DNA
What are the strategies of gene therapy?
Gene replacement/augmentation, delivery of therapeutic protein, gene silencing, killing of cells, immunotherapy, gene editing
How does gene silencing differ from gene editing?
Gene silencing is used to reduce expression of a mutant gene. Conversely, gene editing is altering of an existing gene, which is typically under-expressed.
True/False. Restoring only partial levels of normal proteins will have little therapeutic effect.
False. Restoring even 5-20% of normal protein levels could have a significant therapeutic effect for the patient.
