The present invention provides methods for synthesis and therapeutic use
of DNA and RNA oligonucleotides and analogs. RNA oligonucleotides are
synthesized using a small, circular DNA template which lacks an RNA
polymerase promoter sequence. The RNA synthesis is performed by combining
a circular single-stranded oligonucleotide template with an effective RNA
polymerase and at least two types of ribonucleotide triphosphate to form
an RNA oligonucleotide multimer comprising multiple copies of the desired
RNA oligonucleotide sequence. Preferably, the RNA oligonucleotide
multimer is cleaved to produce RNA oligonucleotides having well-defined
ends. Preferred RNA oligonucleotide multimers contain ribozymes capable
of both cis (autolytic) and trans cleavage.