Cylindrical brush polymers constitute promising polymeric drug delivery systems (nanoDDS). Because of the densely grafted side chains such structures may intrinsically exhibit little protein adsorption (stealth effect) while providing a large number of functional groups accessible for bioconjugation reactions. Polysarcosine (PSar) is a highly water-soluble, nonionic and nonimmunogenic polypeptoid based on the endogenous amino acid sarcosine (N-methyl glycine). Here we report on the synthesis, characterization and biocompatibility of cylindrical brush polymers with either polysarcosine side chains or poly-l-lysine-b-polysarcosine side chains. The latter leads to block copolypept(o)id based core-shell cylindrical brushes with a cationic poly-l-lysine (PLL) core and a neutral polysarcosine corona. The cylindrical brush polymers were prepared by ring-opening polymerization of the respective N-carboxyanhydrides (NCA) from a macroinitiator chain. Preliminary experiments on complex formation with siRNA demonstrate that a core-shell cylindrical brush polymer may complex on average up to 270 RNA molecules amounting to a high loading efficiency of N+/P- = 1.1. No bridging between cylindrical brushes leading to larger aggregates is observed. In vitro studies on the silencing of the expression of ApoB100, which is abundantly expressed in AML-12 hepatocytes, induced by siRNA-cylindrical core-shell brush complexes showed high efficiency, leading to a knock-down efficiency of ApoB100 mRNA of 70%.