Nucleic acid medicines are expected as promising therapeutic agents. While several nucleic acid medicines have already moved forward to clinical trials, it is still eagerly anticipated for treating a diverse range of diseases to develop safe nanocarriers that could deliver nucleic acids efficiently to specific targets in vivo. Conventionally, cationic carriers that interact with nucleic acids electrostatically have been used mainly in vitro, but they are potentially toxic and unstable in vivo. To address these issues, various non-cationic carriers showing higher biocompatibility, higher safety, and in vivo stability have so far been developed as forthcoming nanocarriers, though they often repel nucleic acids electrostatically. In this review, we summarized the current progress in nucleic acid delivery systems, mainly non-cationic nanocarriers. Next, we described a new method for encapsulating high contents of siRNA into non-cationic liposomes, which is simple, feasible, and readily scalable. After arming the surface of liposomes with targeting molecules (e.g., bio-nanocapsule (BNC) harboring hepatitis B virus-derived human hepatocyte-specific infection machinery), they could deliver siRNA into the cells in an active targeting manner. Finally, we discussed the important issues for developing the future nucleic acid delivery technology.