Gene silencing by single-stranded polynucleotides

1. A method for inhibiting expression of a target gene in a tumor cell, wherein the target gene is Casein Kinase 2, comprising: administering a formulation of single stranded polynucleotides to a mammal in an amount sufficient to inhibit expression of the target gene in the tumor cell, wherein said formulation is prepared according to a process comprising:

employing a suitable siRNA design algorithm to identify a candidate functional double stranded siRNA to a target RNA;

synthesizing a single stranded polynucleotide sequence comprising at least a portion of the guidestrand of the candidate functional double stranded siRNA, wherein a functional single stranded polynucleotide consisting of 15-25 linked nucleosides without a self-complementary sequence region is formed; wherein the functional single stranded polynucleotide sequence comprises a 3′ RNA portion and a 5′ DNA portion, wherein the functional single stranded polynucleotide comprises at least three consecutive ribonucleotides at the 3′ end, wherein the functional single stranded polynucleotide is at least 50% DNA, wherein each of the internucleoside linkages of the functional single stranded polynucleotide is a phosphodiester linkage; and

formulating a plurality of the functional single stranded polynucleotides, in the absence of a passenger strand, with a pharmaceutically acceptable non-viral carrier;

wherein the formulation is introduced into the tumor cell,

wherein the functional single stranded polynucleotides of the formulation are delivered to the perinuclear region or the nucleus of the tumor cell,

whereupon said functional single-stranded polynucleotides concurrently activate dsRNAse and RNAseH mechanisms of the cell, thereby inhibiting expression of the target gene in the tumor cell.

2. The method of claim 1 , wherein the functional single stranded polynucleotides do not comprise extrinsic 5′ phosphorylation.