Embodiments described herein provide novel bacterial-based methods, systems, and delivery vehicles capable of delivering DNA, RNA, proteins, and other cargo into targeted mammalian cells, both in vitro and in vivo, with high efficiency. Delivery vehicles may be used to deliver molecules such as prophylactic or therapeutic proteins, DNA, shRNA, DNA vaccines, mucosal vaccines, modified viruses or viral components, and other bioactive molecules. Potential applications include gene therapy, wound healing therapies, cancer therapy, immune modulation, and research applications for which delivery of DNA, RNA, proteins, or other cargo into mammalian cells and tissues is required.