Although oligonucleotide drugs can bind to definite targets very specifically, there are many challenges regarding their delivery including the large size, negative charges, problems in passing through the barriers, such as the plasma membrane, plasma proteins, immune systems, blood-brain barrier and the possibility of renal clearance or nuclease degradation . Modification in different parts of the molecule or bioconjugation with GalNAc or bottlebrush polymers , for instance, are some strategies to relieve these challenges .