Abstract: The present disclosure relates to synthetic oncolytic viruses comprising a lipid nanoparticle comprising one or more types of lipid and a self-amplifying replicon RNA comprising a sequence that encodes an immunomodulatory molecule.

Abstract: Lipid nanoparticle (LNP) encapsulating self-amplifying mRNA, compositions, and methods of using the novel nucleic acid constructs and compositions are disclosed. LNP constructs include novel ionizable lipid. Novel sa-mRNA constructs encode a modified SARS-CoV-2 spike protein, wherein the polynucleotide has been truncated to not include nucleotides encoding a SARS-CoV-2 transmembrane domain and short cytosolic domain amino acids and immunomodulators. Sa-mRNAs are useful in for use as a therapeutic, diagnostic and/or prophylactic agent to mammalian cells or organs.

Abstract: Novel ionizable lipids, compositions, and methods of using the novel ionizable lipids and compositions are disclosed. Lipid nanoparticle compositions include a novel ionizable lipid as well as additional lipids such as phospholipids, structural lipids, and PEG lipids. Lipid nanoparticle compositions further including biologically active agents such as mRNA or DNA are useful in the delivery of biologically active agents to mammalian cells or organs.

Abstract: Disclosed are methods of increasing mitochondrial respiration to treat obesity-related diseases and conditions, such as atherosclerosis, hypertension, diabetes, especially type 2 diabetes (NIDDM (non-insulin dependent diabetes mellitus)), impaired glucose tolerance, dyslipidemia, coronary heart disease, gallbladder disease, osteoarthritis and various types of cancer, such as endometrial, breast, prostate and colon cancers and the risk for premature death as well as other conditions, such as diseases and disorders, which conditions are improved by an increase in mitochondrial respiration. Also disclosed are methods of promoting weight gain, which is achieved by a decrease in mitochondrial respiration. Also disclosed are methods of identifying compounds useful for increasing mitochondrial respiration to treat obesity-related diseases and conditions.

Abstract: The present disclosure relates to synthetic oncolytic viruses comprising a lipid nanoparticle comprising one or more types of lipid and a self-amplifying replicon RNA comprising a sequence that encodes an immunomodulatory molecule.

Abstract: Disclosed herein are genetically modified herpesviruses for the treatment of cancer. Also provided are methods of treating cancer using genetically modified herpesviruses.

Abstract: This disclosure provides engineered genetic systems for sequestering and/or destroying viruses, compositions and cells comprising the genetic systems, and methods of treating viral infections, reducing viral load, and/or reducing viral spread. The disclosure also provides libraries comprising elements to be incorporated into the engineered genetic systems.

Abstract: Genetic circuits have been developed to regulate behaviors of replicon RNA in responses to small molecules, which has broader applications, such as for quantitative expression of cargo genes, temporary expression of immunomodulatory cytokines or antigens for better cancer immunotherapy or vaccination, and for increased safety in use of self-replicating vectors or in combination with other viral-delivery vectors. Described herein are genetic circuits suitable for systems that either require a tight off state or a slow off state, which can serve for instance where either a kill switch or prolonged protein expression (e.g., of vaccine antigens) are needed.

Abstract: The present disclosure relates to synthetic oncolytic viruses comprising a lipid nanoparticle comprising one or more types of lipid and a self-amplifying replicon RNA comprising a sequence that encodes an immunomodulatory molecule.

Abstract: The disclosure provides methods for an in vitro evolution technique to identify and characterize mutations in the non-structural genes of an alphavirus replicon that increase the strength and persistence of expression of the replicon genome. Also provided herein are in vivo methods for administering to an animal model a mutated alphavirus replicon that codes for a gene of experimental or therapeutic interest in the subgenome of the alphavirus replicon. The mutations identified herein improve the therapeutic potential of self-replicating RNA, which may have implications for cancer immunotherapy and beyond, e.g., for vaccination or gene therapy.