The present invention relates to RNAi molecules, and compositions thereof, comprising a 2' internucleoside linkage connecting the nucleotide at position 1 and the nucleotide at position 2 at the 5' end of the antisense strand. Specifically, the invention relates to single- and double-stranded short interfering nucleic acid (siNA) molecules that are capable of mediating RNA interference comprising 5' modified nucleotides that comprise, among other potential modifications, a 2' internucleoside linkage. The invention further relates to 5' modified nucleotides used as reagents to generate the RNAi molecules of the invention and methods of using the disclosed RNAi molecules.