Patent Publication Number: WO2020182869A1
Current Assignee: BIONTECH RNA PHARMACEUTICALS GMBH and TRON
Inventors: Ugur Sahin (CEO), et al
Title of invention: Therapeutic rna for prostate cancer
patents.google.com/patent/WO…
This patent states:
“In gonads, plasmid DNA was either not detected or samples were slightly above the LLOD, suggesting that there is only a minor risk of integration of plasmid residues, e.g., the Kanamycin resistance gene into the genome of germline cells.”
This assessment is based on the limited scope of the Kanamycin resistance gene (qPCR) and does not comprehensively consider the effects of all residual DNA.
The description of “only a minor risk” in the patent suggests that even at extremely low levels near the limit of detection (LLOD), the possibility of genomic integration cannot be completely excluded in theory.
Should such a recognition be regarded as negligible.
According to this description, if residual DNA, particularly fragments derived from plasmids, is efficiently delivered into cells by LNP, it may enter the nucleus, including the possibility that sequences similar to the SV40 promoter/enhancer may contribute to nuclear transport, and could be integrated into the genome through mechanisms such as Non-homologous end joining. This possibility cannot be ruled out in theory.
In particular, if such an event were to occur in germline cells, there is a potential risk that genetic changes could be inherited by offspring as heritable mutations.