*Seminar Series: Brisbane Developmental Biology Seminar Series
*Location: Large Seminar Room, QBP (Building #80)
*Date: 09/05/2017
*Time: 16:00

Speaker #1 details
*Title of talk: Solutions for cell therapy safety with genome editing
*Speaker's name: Prof Andras Nagy
*Speaker's organisation: Lunenfeld-Tanenbaum Research Institute, Toronto, Canada and ARMI, Monash University, Melbourne, Australia
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Talk Abstract: Numerous human pluripotent stem cell-based therapies are currently on their way to treat devastating degenerative diseases. However, concerns about the safety holds back the full utilization of these promising new treatments. Here we introduce a concept and show the associated genome engineering strategy that addresses this issue and provides a solution for fail-safe cell therapies.
To ensure the reliable expression of a suicide transgene system in proliferating cells, we transcriptionally linked it to a cell division essential endogenous locus (CDEL) in a homozygous manner. Our prototype suicide gene was the herpes simplex virus-thymidine kinase (HSV-TK), and the prototype CDEL was Cdk1. The coding regions of these two kinases were connected with a viral 2A sequence by CRISPR/Cas9 assisted genome editing. We generated mouse and human embryonic stem cell lines with the above homozygous modification of the Cdk1 locus. Our results showed that we could ablate proliferating cells both in vitro and in vivo by ganciclovir treatment, the pro-drug for HSV-TK. The elimination of proliferating cells could efficiently stop the growth of teratomas generated by these ES cells and rendered this tissue to dormancy.Using published and our own experimental measures of forward mutation rates, we defined the cell population-based fail-safe level for different genome alteration designs (genotypes). Then we mathematically modeled the probability of escape from our fail-safe cell systems during expansion of cells to a number that might be needed for clinical use. Depending on the scenarios of different types of cell therapies, this concept - in combination with another optional safety strategy developed in my lab - will provide versatile options that meet the complex needs for the safety of future cell-based therapies.
By solving the hurdle of cell therapy safety, we have opened a gate for designing novel cells with therapeutic functions and using them to treat or even cure degenerative diseases. This new space in medical research is expected to be transformative in our near-future medicine.
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Speaker #2 details
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Other Details:
*Host name: Josephine Bowles
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*Host email: jo.bowles@uq.edu.au