**4.2 Cholesterol**

A 29 nucleotide-log 2′-F pyrimidine modified RNA aptamer was reported to inhibit Hepatitis C virus (HCV) replication *in vitro*. In the follow-up study, this aptamer was derivatized with cholesterol to form cholesterol aptamer conjugate (chol-aptamer). This conjugate entered the cell and inhibited HCV RNA replication in a cell-based system successfully. Systemic administration of chol-aptamer was well tolerated by mice and increased retention time in plasma [14].

## **4.3 Dialkyl lipids**

Willis et al. conjugated diacylglycerol (DAG) to the 5′-end of a nuclease resistant VEGF aptamer [40]. This DAG-aptamer conjugate was then incorporated to a liposome bilayer, which resulted in aptamers with improved anti-VEGF activity *in vitro* and *in vivo*, both. Importantly, this DAG-aptamer-liposome complex had a considerably better residence time in plasma as compared to unmodified aptamer [40].
