(R-X-R) 4 -PMO conjugates with X spacers of increasing lengths (from 2 to 8 atoms) ( Figure 1A ) have thus been compared in terms of affinity for a model heparan sulfate on a Hi-trap Heparin column ( Figure 1B ). Increasing spacer length leads to decreased affinity as monitored by the NaCl concentration required for elution in keeping with published data (20) . Conjugates in this series were then compared for their ability to promote splicing correction in dose-response experiments ( Figure 1C and data not shown). Increasing the length of the spacer led to increased luciferase expression with an optimum for the C5-linked material.