RNA interference (RNAi) is a biological response to double-stranded RNA that regulates expression of protein-coding genes and is a natural mechanism for gene silencing. Delivery of short, interfering RNA (siRNA) leads to RNAi of the targeted genes.
Several viral epidemics – such as the epidemics caused by H1N1 influenza virus, human immunodeficiency virus (HIV), Ebola virus, Zika virus, severe acute respiratory syndrome (SARS) virus, Middle East respiratory syndrome (MERS) virus and SARS-CoV-2 – have profoundly impacted global human health. Early identification of infected and/or infectious persons and isolating them from the population are some of the most effective and evident measures to prevent human-to-human spreading.
The promise of RNA interference based therapeutics is made evident by the recent surge of biotechnological drug companies that pursue such therapies and their progression into human clinical trials. The present invention discloses novel RNA and RNA/DNA nanoparticles including multiple siRNAs, RNA aptamers, fluorescent dyes, and proteins. These RNA nanoparticles are useful for various nanotechnological applications.
RNA nanoparticles have the potential to serve as excellent drug or imaging delivery systems due to their designability and versatility. Furthermore, the RNA nanoparticles of the invention are also capable of self-assembly and potentially form nanotubes of various shapes which offer potentially broad uses in medical implants, gene therapy, nanocircuits, scaffolds and medical testing.
RNA interference (RNAi) is a naturally occurring post-transcriptional gene regulation process that represses the expression of specific genes. Exploiting endogenous RNAi by externally-delivered small-interfering RNA (siRNA) is a promising therapeutic for the treatment of various diseases representing several major unmet medical needs.
Current treatments for cancer and viral infection are limited remedies that often suppress cell or viral replication rather than eliminate diseased cells entirely from the body. A further limitation is that these therapies often compromise healthy cells as well, leaving problems of recurrence and side effects.
Researchers at developed a novel therapeutic nanoparticle (NP) system harboring therapeutic small siRNA that can significantly enhance effectiveness and specificity of treatments by killing diseased cells.
This technology provides improved processes for production and purification of nucleic acid-containing compositions, such as non-naturally occurring viruses, for example, recombinant polioviruses that can be employed as oncolytic agents. Some of the improved processes relate to improved processes for producing viral DNA template.
Nanoparticles such as lipid-based nanoparticles (LNPs) represent a relatively new era of targeted drug delivery systems wherein these biocompatible particles can carry the drug(s) of interest to a specific tumor site. The new generation of nanoparticles, known as stealth nanoparticles, are engineered to have a coating of polyethylene glycol polymer (PEG) or other glycolipids that enable them to evade the immune system and have a longer circulation lifespan as well as improved bioavailability to diseased tissue and reduced non-specific toxicity.
The manner by which cancers evade the immune response is not well-understood. What is known is that the manner is an active process that regulates immune responses employing at least two types of suppressive cells, myeloid-derived suppressive cells and regulatory T cells (Tregs), a key subset of CD4+ T cells that controls peripheral tolerance to self- and allo-antigens. Tregs are considered to play a key role in the escape of cancer cells from anti-tumor effector T cells.
Regulatory B-cells (Breg) play an important role in reducing autoimmunity and reduced levels of these cells are implicated in etiology of several auto-inflammatory diseases. Despite their impact in many diseases, their physiological inducers are unknown. Given that Bregs are a very rare B-cell, identifying factors that promote their development would allow in vivo modulation of Breg levels and ex-vivo production of large amounts of antigen-specific Bregs to use in immunotherapy for auto-inflammatory diseases.