What is vector shedding?
The release of the virus from the body, into the environment, through secretions/excretions of the patient treated with a viral vector
This is the most commonly used class of drugs for immunosuppression in AAV gene therapy programs?
Corticosteroids
In gene therapy, a cell is said to be transduced when it delivers what to the target cell or tissue?
genetic material/payload
Which gene therapy route of administration is low risk but requires high dose?
IV
What is an extra or special consideration for nonclinical studies for Cell and Gene Therapy Programs?
Answers may vary; need to identify a clinical dose that provides some benefit while maintaining margin for safety
What is the typical period of time for which vector shedding is collected post dosing in a gene therapy trial?
3 consecutive negatives before no longer required
What immune response is an Elispot test being used to evaluate?
cell mediated immune response
Daily Double! (worth 2x points)
The current follow up period for a gene therapy product that integrates into the patient’s cell genome is how long?
15 years
Which route of administration provides high brain transduction, low spinal cord transduction but may be given at a lower dose?
ICV
What is one reason oncology and rare disease account for the majority of CGT research?
risk/benefit profile
Name 2 import factors for consideration when choosing the serotype of an AAV.
Tropism---right vector for target tissue/cells, NAb prevalence
What laboratory test is performed typically at screening to assess a participant’s potential for an immune response to the vector?
NAbs
Genes delivered outside and transferred back into the body is this type of gene therapy approach.
ex vivo
Which route of administration provides high brain transduction, high spinal cord transduction but may be given at a lower dose?
ICM
What US government agency provides guidelines for an IBC?
NIH
A viral vector is integrating when it does this.
DNA integrates into the host cell genome making a permanent change, all daughter cells will have the new DNA
Tacrolimus is an immunosuppressant that is most likely to interfere with this type of immune response.
adaptive immune response
What is an allogeneic cell therapy?
donor/off the shelf cell therapy
Name one advantage to using direct deliver administration to the target tissue?
lower dose, may avoid NAb in blood
For CGT studies, this is the most common rate limiting step for site activation.
contract execution
Which viral vector can deliver only small genes, sometimes called micro, or mini versions of the gene?
AAV
Immunosuppressive drugs can influence both the _____ and ______ of the gene therapy product.
safety and efficacy
What is gene editing?
DNA is modified at a particular location in the genome to insert/replace/remove a portion to create a desired edit in the DNA to “correct” the gene of interest
Name 3 routes of administration used in AAV gene therapies.
IV, ICM, ICV, IT, IO, etc.
What risk is an IBC focused on?
risk to research staff/environment