Expert: Florence M Rollwagen - 8/15/2008

Question
do you think it is possible for any type of oligonucleotide to be absorbed into gastric cells (eg by complexing to ethanol or aspirin), without prior acid hydrolysis?

Answer
Hi Caroline:  Thanks for your question.


To answer your question we first have to define oligonucleotide.  Cells will readily take up small nucleotides, such as AMP (adenosine monophosphate, a precursor to the energy molecule ATP).  Larger oligonucleotides of longer chain length will vary by composition and thereby affect uptake.

"http://jn.nutrition.org/cgi/reprint/124/1_Suppl/131S.pdf"

There is some information on oligonucleotide uptake by intestinal cells in tissue culture, at neutral pH.   In the gastric low pH environment, several studies in rodents "http://www.ncbi.nlm.nih.gov/pubmed/7646565", "http://www3.interscience.wiley.com/journal/107641385/abstract",
and humans "http://www.ncbi.nlm.nih.gov/pubmed/17721945", "http://www3.interscience.wiley.com/journal/115806918/abstract", have been published.

I couldn’t find anything on aspirin stabilization of oligonucleotides, though.  The papers mentioned above did not modify the oligos, but some did use a permeant to allow better entry.

I hope this answer has helped you.  Please write back if you have more questions.

FM Rollwagen, PhD