Derivatized oligonucleotides having improved uptake and other properties

DETAILED DESCRIPTION OF THE INVENTION Antisense therapeutics can be practiced in a variety of organisms ranging from unicellular prokaryotic and eukaryotic organisms to multicellular eukaryotic organisms.
Any organism that utilizes DNA-RNA transcription or RNA-protein translation as a fundamental part of its hereditary, metabolic or cellular control is susceptible to antisense therapeutics and/or prophylactics.
Seemingly diverse organisms such as bacteria, yeast, protozoa, algae, all plant and all higher animal forms, including warm-blooded animals, can be treated by antisense therapy.
Further, since each of the cells of multicellular eukaryotes also includes both DNA-RNA transcription and RNA-protein translation as an integral part of its cellular activity, antisense therapeutics and/or diagnostics can also be practiced on such cellular populations.
Furthermore, many of the organelles, e.
g.
, mitochondria and chloroplasts, of eukaryotic cells also include transcription and translation mechanisms.
As such, single cells, cellular populations or organelles can also be included within the definition of organisms that are capable of being treated with antisense therapeutics or diagnostics.
As used herein, therapeutics is meant to include both the eradication of a disease state, killing of an organism, e.
g.
, bacterial, protozoan or other infection, or control of erratic or harmful cellular growth or expression.
While we do not wish to be bound by any particular theory, it is believed that the presence of many nuclear proteins in the nucleus is due to their selective entry through the nuclear envelope rather than to their selective retention within the nucleus after entry.
By this mechanism, the nucleus is able to selectively take up certain proteins and not others.
The uptake is based upon the sequence of the peptide or protein, which provides a selective signal sequence that allows accumulation of the peptide or protein in the nucleus.
One such peptide signal sequence is found as part of the SV40 large T-antigen