Measuring oligonucleotide uptake

From: H. Elizabeth Broome, M.D. (ebroome@UCSD.Edu)
Date: Wed Mar 17 1999 - 12:30:04 EST


I would like to determine which subset of cells have taken up an antisense
oligonucleotide, and to what extent.  Does anyone have a good method for
this?  I have tried cotransfecting my cells with a FITC labeled irrelevant
oligo (a preliminary study before getting the actual antisense oligo
labeled), and I got what looks like a lot of non-specific labeling of the
cells.  I assume this is due to sticking of the fluorescent oligo on the
surface of the cells.  The dead cells took up even more of the fluorescent
oligo.  Basically, the fluorescent oligo was a good label of dead cells. In
fact, when I labeled the cells with ethidium monoazide and fixed them, I
got an interesting result (at least to me).  In the control cells without
the FITC oligo, the dead cells stained with EMA were moderately fluorescent
in the FL2 channel.  The same dead cells with the FITC oligo were very
negative for FL2, but had the bright FL1 staining from the FITC.  Could
there be some quenching going on?  If so, I was wondering whether it might
be possible to use this quenching phenomenon to identify live cells that
had taken up the oligo.  For instance, could you have the cells
constitutively expressing a fluorescent marker, and then transfect them
with the fluorescent oligo and see which cells quenched?
H. Elizabeth Broome, M.D.
Department of Pathology
University of California, San Diego
9500 Gilman Drive #0612
La Jolla, CA 92093

ebroome@ucsd.edu

Phone	(619) 534-5216
FAX	(619) 534-7415



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