دانلود مقاله : 

Rosemary Broome, Jonathan Liu, Dominic Justewicz, Mark S. GalinskiRapid clearance of intranasally administered DNA from rat tissues 2013

 نویسندگان :

David E. Tabor , Sachin Mani, Xuan Shen, Xiaomu Chen, Charles Engbers, Scott Jacobson, Rosemary Broome, Jonathan Liu, Dominic Justewicz, Mark S. Galinski

چکیده : 

The cold-adapted (ca) live attenuated influenza vaccine (LAIV) strains are manufactured in embryonated

hens’ eggs. Recently, a clonal isolate from Madin Darby Canine Kidney (MDCK) cells was derived and

characterized to assess its utility as a potential cell substrate for the manufacturing of LAIV [1]. Since

MDCK cells are a transformed continuous cell line [2], and low levels of residual cellular components

(DNA and protein) are found in the intermediates and final filled vaccine, we sought to characterize the

uptake and clearance of MDCK DNA from tissues in order to assess theoretical risks associated with

manufacturing LAIV in MDCK cell culture.

In order to address this concern, MDCK DNA uptake and clearance studies were performed in Sprague

Dawley rats. DNA extracted from MDCK Master Cell Bank (MCB) cells was administered via an intranasal

(IN) or intramuscular (IM) route. Tissue distribution and clearance of MDCK DNA were then examined in

fourteen selected tissue types at selected time points post-administration using a quantitative PCR assay

specific for canine (SINE) DNA.

Results from these studies demonstrate that the uptake and clearance of MDCK DNA from tissues vary

depending on the route of administration. When DNA was administered intranasally, as compared to

intramuscularly, detectable DNA levels were lower at all time points. Thus, the intranasal route of vaccine

administration appears to reduce potential risk associated with residual host cell DNA that may be

present in cell culture produced final vaccine products.

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