Ribonucleic acid (RNA) nanotechnology provides a new approach for the treatment and detection of disease, and is one of the most promising applications for overcoming disease. The goal of nanotechnology-based RNA therapy is to provide a safe, efficient and specific nonpathogenic nanodevice for the delivery of multiple therapeutic RNAs, including siRNA, aptamers, ribozymes, antisense RNA, molecular beacons, and sensors.
The rapidly expanding field of nanobiology opens up the possibilities for the development of new methods and compositions that can be used for the diagnosis, prognosis, and treatment of various diseases such as cancer. While an increasing number of novel drugs and therapeutic agents are being discovered, the problem of delivering them specifically to the desired site or cell has not been solved. Nanoparticles are ideal drug delivery devices due to their novel properties and functions and ability to operate at the same scale as biological entities. Nanoparticles, because of their small size, can penetrate through smaller capillaries and are taken up by cells, which allow efficient drug accumulation at the target sites.
Yingling's and Shapiro's invention is based on the discovery of multifunctional-engineered nanoparticles. They discovered polyvalent RNA nanoparticles comprising RNA motifs as building blocks that can form RNA nanotubes. The polyvalent RNA nanoparticles are suitable for therapeutic or diagnostic use in a number of diseases or disorders. Specifically, the invention provides RNA nanostructures comprising RNA Ii-like or RNA IIi-like that have multiple positions available for conjugation of, for example, therapeutic agents or diagnostic agents, such as imaging agents.
Advantageously, the nanoparticles developed by Yingling and Shapiro provide a number of improvements over nanoparticles currently available. For example, the RNA nanoparticles of the invention may not induce a significant immune response like the protein nanoparticles currently used. Moreover, the nanoparticles of the invention are smaller than many currently available nanoparticles and therefore allow for increased efficiency of administration. The nanoparticles comprise multiple RNA subunits each of which has the ability to bind, for example, a therapeutic or diagnostic agent.
Moreover, multiple different agents can be present within a single nanoparticle. In an exemplary embodiment, the RNA nanoparticle comprises one or more agents that will specifically target the nanoparticle to a particular type of cell and one or more therapeutic agents. A specific example of this type of nanoparticle would have an agent that specifically targets a particular type of cancer cell with one or more cancer therapeutic agents. Previous studies have shown that RNA nanostructures are effective drug delivery vehicles.
The RNA nanoparticles provide novel drug delivery compositions that are capable of transport across biological barriers. Moreover, the nanoparticles may not elicit a significant immune response, or elicit only a low-level immune response and are therefore advantageous for administration to subjects.
The RNA nanoparticles have the ability to assemble, e.g., self-assemble, in to higher order structures, e.g.,. a ring or a nanotube. Exemplary RNA nanoparticles that have the ability to self-assemble into nanotubes are hexomeric RNA nanoparticles comprising RNA Ii and/or RNA IIi motifs. RNA nanotubes have use in, for example, nanocircuits, medical implants, gene therapy, scaffolds and medical testing.
Although protein nanoparticles are widely used and researched for therapeutic and diagnostic purposes, protein nanoparticles have been shown to elicit an immune response in animals that makes them difficult to use for long-term administration. Conversely, protein free RNAs elicit only a low level immune response, and therefore, are more practical for long-term administration. Thus all-RNA nanoparticles can be used in long-term treatment of chronic diseases such as cancer, hepatitis B, or AIDS. RNA is immune to nuclease degradation. A limiting factor for RNA nanoparticles is their stability in the bloodstream and nonspecific cellular uptake, posing a requirement of high dosage. The relative stability can be controlled by the chemical modification of the backbone, addition of proteins, lipids, self-contained compact structures or polymeric chains. Yingling and Shapiro believe they have overcome these limitations.
The nanoparticle compositions developed by Yingling and Shapiro can be administered to an individual (such as human) via various routes, such as parenterally, including intravenous, intra-arterial, intraperitoneal, intrapulmonary, oral, inhalation, intravesicular, intramuscular, intra-tracheal, subcutaneous, intraocular, intrathecal, or transdermal. For example, the nanoparticle composition can be administered by inhalation to treat conditions of the respiratory tract. The composition can be used to treat respiratory conditions such as pulmonary fibrosis, broncheolitis obliterans, lung cancer, bronchoalveolar carcinoma, and the like. In some embodiments, the nanoparticle composition is administrated intravenously and in others the nanoparticle composition is administered orally.
The dosing frequency of the administration of the nanoparticle composition depends on the nature of the therapy and the particular disease being treated. For example, dosing frequency may include, but is not limited to, once daily, twice daily, weekly without break; weekly, three out of four weeks; once every three weeks; once every two weeks; weekly, two out of three weeks.
The dosing frequency of the administration of the nanoparticle composition depends on the nature of the therapy and the particular disease being treated. For example, dosing frequency may include, but is not limited to, once daily, twice daily, weekly without break; weekly, three out of four weeks; once every three weeks; once every two weeks; weekly, two out of three weeks.
