Morpholinos with Increased Delivery Efficiency

Morpholino antisense oligos (Morpholinos) are a class of synthetic non-ionic molecules, each designed to very specifically bind to a selected complementary RNA sequence (targeted RNA transcript). Custom-sequence Morpholinos are used in a broad range of biological research areas, as well as for therapeutic applications in vivo (in living animals such as humans).For most in vivo applications the "bare" Morpholino (FIG. 1a) is linked to a cationic delivery component to give a "delivery-enabled" Morpholino (FIG. 1b) with significantly improved delivery efficiency. However, cytosolic delivery was still markedly less than expected. Then recently we discovered that by adding a special disconnect component between the Morpholino component and the cationic delivery component (FIG. 1c), the cytosolic delivery efficiency for the Morpholino was dramatically increased (about a 1,000% increase in delivery efficiency).This patent application describes designing, making, and using such delivery-enabled Morpholinos containing a key disconnect component.