This Small Business Innovation Research (SBIR) Phase I project proposes to develop novel superparamagnetic biocompatible cell-penetrant bioactive nanoparticles for reprogramming human somatic cells and generation of pluripotent stem cells with intact genomes. To demonstrate technical feasibility, the plan is to use the most promising routes for high-density functionalization of nanoparticles. The resultant superparamagnetic biocompatible bioactive nanoparticles (SPBBN) will be evaluated for their efficiency in cell reprogramming and generation of induced pluripotent stem cells. The goal is to obtain the proof-of-concept data documenting that SPBBN produced by coupling cell penetrant and biologically active molecules can be used successfully for generation of pluripotent stem cells and other cell types with intact genomes, thereby suitable for research and preclinical/clinical applications.
The broader impact/commercial potential of this proposed project is the production of superparamagnetic biocompatible bioactive nanoparticles (SPBBN) capable of penetrating through cell membrane and delivering biologically active molecules to reprogram cells into stem or more specialized cells while preserving the cell genome intact. Because this innovative methodology does not use DNA or RNA, the resultant human pluripotent stem cells (PSCs) and/or their progeny will have an intact genome, and, therefore, will preserve their normal gene expression profiles. There is a lack of alternative, effective non-integrating technology; a vast majority of research laboratories in academia and private centers generate human PSCs using viral delivery of reprogramming factors. Furthermore, advances in personalized medicine are also hindered by the absence of effective cell reprogramming and generation of safe PSCs and their progeny. The company's unique approach offers cell membrane-penetrant bioactive nanomaterials for cell reprogramming solutions focused on cellular therapy for academic research and pharmaceutical preclinical and clinical applications.
This Small Business Innovation Research (SBIR) project focused on development of novel superparamagnetic cell-penetrant bioactive nanoparticles suitable for reprogramming human somatic cells and generation of pluripotent stem cells with intact genomes. To demonstrate technical feasibility, different routes for high-density functionalization of nanoparticles were evaluated. The resultant functionalized superparamagnetic bioactive nanoparticles were evaluated in various assays and demonstrated the lack of cytotoxicity as well as efficient penetration through cell membrane and delivery of bioactive small and large molecules into the cytoplasm of various human cell types. The generated functionalized nanoparticles produced by coupling cell penetrant and biologically active molecules are suitable for research and preclinical/clinical applications. The broader impact/commercial potential of this project is the production of superparamagnetic bioactive nanoparticles capable of penetrating through cell membrane and delivering biologically active molecules inside the cells while preserving the cell genome intact. Because this innovative methodology is not toxic to human cells and does not use DNA or RNA, it is superior to viral or lysosomal delivery of bioactive molecules commonly used by numerous research laboratories in academia and private sector interested in targeted control of cell fate and various properties. The company's unique proprietary nanobiotechnology offers novel functionalized cell membrane-penetrant bioactive nano-materials for intracellular delivery of various biologics and therapeutic agents and is suitable for academic research and pharmaceutical preclinical and clinical applications.
