TY - JOUR
T1 - Cre Recombinase Mediates the Removal of Bacterial Backbone to Efficiently Generate rSV40
AU - Shi, Xiaoxia
AU - Ykema, Matthew Ryan
AU - Hazenoot, Jaco
AU - ten Bloemendaal, Lysbeth
AU - Mancini, Irene
AU - Odijk, Machteld
AU - de Haan, Peter
AU - Bosma, Piter J.
PY - 2018
Y1 - 2018
N2 - Gene therapy has been shown to be a feasible approach to treat inherited disorders in vivo. Among the currently used viral vector systems, adeno-associated virus (AAV) vectors are the most advanced and have been applied in patients successfully. An important drawback of non-integrating AAV vectors is their loss of expression upon cell division, while repeating systemic administration lacks efficacy due to the induction of neutralizing antibodies. In addition, a significant percentage of the general population is not eligible for AAV-mediated gene therapy due to pre-existing immunity. Development of additional viral vectors may overcome this hurdle. Simian virus 40 (SV40)-derived vectors have been reported to transduce different tissues, including the liver, and prevalence of neutralizing antibodies in the general population is very low. This renders recombinant SV40 (rSV40) vector an interesting candidate for effective (re-)administration. Clinical use of SV40 vectors is in part hampered by less advanced production methods compared to AAVs. To optimize the production of rSV40 and make it better suitable for clinical practice, we developed a production system that relies on Cre recombinase-mediated removal of the bacterial plasmid backbone.
AB - Gene therapy has been shown to be a feasible approach to treat inherited disorders in vivo. Among the currently used viral vector systems, adeno-associated virus (AAV) vectors are the most advanced and have been applied in patients successfully. An important drawback of non-integrating AAV vectors is their loss of expression upon cell division, while repeating systemic administration lacks efficacy due to the induction of neutralizing antibodies. In addition, a significant percentage of the general population is not eligible for AAV-mediated gene therapy due to pre-existing immunity. Development of additional viral vectors may overcome this hurdle. Simian virus 40 (SV40)-derived vectors have been reported to transduce different tissues, including the liver, and prevalence of neutralizing antibodies in the general population is very low. This renders recombinant SV40 (rSV40) vector an interesting candidate for effective (re-)administration. Clinical use of SV40 vectors is in part hampered by less advanced production methods compared to AAVs. To optimize the production of rSV40 and make it better suitable for clinical practice, we developed a production system that relies on Cre recombinase-mediated removal of the bacterial plasmid backbone.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85056610811&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/29766030
U2 - https://doi.org/10.1016/j.omtm.2018.02.010
DO - https://doi.org/10.1016/j.omtm.2018.02.010
M3 - Article
C2 - 29766030
SN - 2329-0501
VL - 9
SP - 225
EP - 233
JO - Molecular therapy. Methods & clinical development
JF - Molecular therapy. Methods & clinical development
ER -