Functionalizing Morpholino Oligos for Antisense Drug Research and Development

A Morpholino oligo itself is difficult to physically detect in a biological assay system, and is also poorly cell-permeable in cultures and living animals. This article provides an overview of the state of the art for solving these problems using corresponding functionalizations. Modification at the ends of a Morpholino oligo gives functional groups or functional entities; the former are useful for further conjugation with custom-designed molecules, whereas the latter may provide fluorophores for optical detection or delivery-enabling moieties for in vivo antisense activity studies. The combination of both ends, in particular with double functionalization at the 3'-end, yields myriad opportunities for more diverse applications. In addition, a photo-cleavable linker inserted into a Morpholino oligo enables control of gene expression in a spatially and temporally controllable manner.