Interaction between foreign DNA and SECs (scavenger endothelial cells) in vitro and in vivo
Contrary to a still dominant dogma, ingested DNA/RNA, in food/feed, is only partially digested and may be taken up in/from the intestines. Subsequently, nucleic acid fragments may enter the bloodstream. Scavenger endothelial cells (SEC), lining the liver sinusoids of the mammalian liver, play an important role in the clearance and degradation of blood-borne soluble waste macromolecules. Preliminary results indicate that this may include DNA. Recent data suggest the existence of degradation “failures” for some types of circulating foreign DNA, which may lead to the incorporation of fragments of foreign DNA into the genome of the host organism. This represents an important problem concerning the safety of GM (genetically modifi ed) food/feed, gene therapy and DNA vaccination.
The main purpose of the proposed project is to elucidate the interactions between foreign DNA and SEC. Experiments will be performed to determine the receptor-ligand specifi cities, routes of internalisation, intracellular transport, and catabolism. Experiments will also focus on conditions and environmental factors, i.e. chemical pollutants which may alter the intracellular traffi cking of endocytosed DNA and thus favor integration of foreign DNA into the genomes of pig, rat, cod and salmon. The results obtained will give valuable basic as well as risk assessment-associated knowledge of practical importance.