Nucline 5-3 is an "on/off" switch on an RNA molecule.
Download PharmaGenomics article PDF.
I. Molecular Design:
Nucline 5-3 is a full length RNA molecule (200-3000 base pairs) with
antisense molecules (20-200 base pairs) bound to the 5' UTR end preventing translation. The 5' UTR contains a short sense
sequence of the mRNA to be detected. When the full-length sense mRNA is present in a cell, the antisense molecule is competed
off of the Nucline molecule through hybridization. Once the antisense molecule is removed, the ribosome translates the Nucline-encoded
protein.
II. Pharmacological effects:
NUCLINE RNA codes for a new protein. Nucline re-programs
the cells to express the new protein.
NUCLINE RNA is expressed when target mRNA is present. Protein synthesis
is not blocked as in RNAi.
NUCLINE RNA responds to specific genes individually or combinations of specific genes.
E.g. Nucline can be designed to respond when IL-2, IL-4 and IL-5 are all present in a cell, but not when just one or two of
the combination is present. Nucline RNA performs Boolean algebra in a living cell.
NUCLINE RNA is sensitive to
the absolute mRNA copy number present in the cell. Nucline can target overexpression of normal genes.