In-Vivo Degradation of DNA-Based Therapeutic BC 007 in Humans

DNA 治疗药物 BC 007 在人体内的降解

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作者:Hanna Davideit, Susanne Becker, Johannes Müller, Niels-Peter Becker, Peter Göttel, Ayşe Abay, Angela Sinn, Matthias Grossmann, Markus Mallek, Annekathrin Haberland, Hardy Weisshoff

Conclusion

Fast and full degradation of BC 007, shown by nucleic bases degradation products, is one of the first reports about the fate of a ssDNA product in humans.

Methods

1H-NMR was applied for n-x degradation product search and beta-aminoisobutyric acid (bAIBA) measurement in urine; ultra-performance liquid chromatography-mass spectrometry was also used for the latter. Colorimetric assays were used for quantification of uric acid in serum and urine.

Results

Fast degradation prohibited the detection of the intermediate n-x degradation products in urine using 1H-NMR. Instead, NMR revealed a further downstream degradation product, bAIBA, which was also detected in serum shortly after initial application. The purine degradation product, uric acid, confirmed this finding of fast metabolism.

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