Disclosed are a polynucleotide with improved stability in vivo, a producing method thereof, and a method of improving the stability of polynucleotide in vivo.

Provided is a method for preparing an oligonucleotide with a ribonucleic acid (RNA) ligase. The RNA ligase includes any one or more enzymes of RNA ligase families Rnll, Rn12, Rn13, and Rn15, and the oligonucleotide includes natural RNA or non-natural RNA. The method may solve the problem that in the prior art, it is difficult to efficiently synthesize a non-natural RNA strand, and the method is suitable for the field of RNA synthesis.

The disclosure provides for ribozyme-mediated fusion constructs and systems and methods thereof, for use in a variety of applications, including for inducible gene expression systems, gene therapy, and combinatorial screening.