Abstract: The present invention relates to compositions and methods for inducing an immune response against influenza virus in a subject. In some embodiments, the present invention provides a composition comprising a nucleoside-modified nucleic acid molecule encoding at least one influenza virus antigen, such as a hemagglutinin antigen or a fragment thereof, neuraminidase antigen or a fragment thereof, nucleoprotein antigen or a fragment thereof, matrix protein 1 antigen or a fragment thereof, or matrix-2 ion channel antigen or a fragment thereof.

Abstract: The present invention relates to compositions for effective delivery of gene editing agents to a target cell, as well as methods of use thereof for the treatment of a disease or disorder.

Abstract: Disclosed herein are methods of increasing the potency of nucleic acid loaded lipid nanoparticles (naLNPs) through certain novel and surprisingly superior LNP manufacturing techniques. Also disclosed are pharmaceutical compositions containing naLNPs manufactured according to the manufacturing methods described herein. The methods disclosed herein overcome major technical difficulties and high costs associated with previous LNP manufacturing techniques. The methods disclosed herein, therefore, greatly improve the industrial production of LNPs in unexpected ways thereby providing more potent naLNPs for nucleic acid delivery. Specifically, the invention disclosed herein are methods that show increased potency naLNPs due to increased mixing concentration of the lipids and mRNA during assembly.

Abstract: The present invention provides compositions for the prevention and treatment of genital herpes, comprising nucleoside modified mRNAs that encode herpes simplex virus (HSV) glycoproteins, including those involved in virus entry and immune evasion, and methods of use thereof.

Abstract: The present invention relates to compositions and methods for inducing an adaptive immune response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a subject. In certain embodiments, the present invention provides a composition comprising a nucleoside-modified nucleic acid molecule encoding a SARS-CoV-2 antigen, adjuvant, or a combination thereof. For example, in certain embodiments, the composition comprises a vaccine comprising a nucleoside-modified nucleic acid molecule encoding a SARS-CoV-2 antigen, adjuvant, or a combination thereof.

Abstract: The present invention provides compositions and methods for reprogramming somatic cells using purified RNA preparations comprising single-strand mRNA encoding an iPS cell induction factor. The purified RNA preparations are preferably substantially free of RNA contaminant molecules that: i) would activate an immune response in the somatic cells, ii) would decrease expression of the single-stranded mRNA in the somatic cells, and/or iii) active RNA sensors in the somatic cells. In certain embodiments, the purified RNA preparations are substantially free of partial mRNAs, double-stranded RNAs, un-capped RNA molecules, and/or single-stranded run-on mRNAs.

Abstract: The invention includes lipid nanoparticles (LNP) capable of eliciting a modulated immune response against an antigen in a subject. The LNPs comprise: (a) at least one first nucleoside-modified ribonucleic acid (RNA) encoding an antigen; (b) at least one second nucleoside-modified RNA encoding a cytokine or immune receptor (such as but not limited to a cytokine receptor); and (c) at least one ionizable lipid. The invention also includes pharmaceutical compositions comprising the LNP of the invention, as well as a method of eliciting a modulated immune response against an antigen in a subject, the method comprising administering an effective amount of a pharmaceutical compositions comprising the LNP of the invention.

Abstract: The invention encompasses novel ionizable lipids compounds and their use in lipid nanoparticles delivery systems that are useful in the delivery of nucleic acids to a mammalian subject that can be included for use, for example, as cancer vaccines, gene editing therapeutics, delivery of nucleic acid (e.g., mRNA) encoding antibodies, vaccines for infectious disease, and protein replacement therapeutics. Additionally, the invention encompasses compositions and therapeutics comprising the ionizable lipids in the lipid nanoparticles and the use of the composition and therapeutics for the preparation of a pharmaceutical composition, especially a vaccine, (e.g., for use in the prophylaxis or treatment of infectious diseases, tumor or cancer diseases, rare diseases, allergies, or autoimmune diseases). The invention encompasses methods of treatment or prophylaxis of the aforementioned diseases.

Abstract: Described herein, in part, are bisphosphonate lipid compounds, lipid nanoparticles (LNPs) thereof, and methods of use thereof. In various embodiments, the LNP selectively targets a cell of interest (e.g., a bone cell and/or bone marrow cell, such as a stem cell, stroma cell, osteoblast, osteocyte, osteoclast, bone lining cell, local mesenchymal cell, progenitor cell, mononuclear blood-borne precursor cell, B cell, endothelial cell, granulocytes, T cell, monocytic lineage, B cell lineage, monocytes, cancer cell, tumor cell, tumor cell that metastasize to bone, blood cancer cell, and multiple myeloma cell, inter alia). In other aspects, the present disclosure relates to methods for in vivo delivery of therapeutic agents to prevent or treat diseases, disorders, or conditions using the LNP compositions of the disclosure.

Abstract: A solution has been discovered that provides a more effective Coronavirus vaccine. The solution is an mRNA vaccine encoding a SARS-CoV-2 nucleoprotein (N) (mRNA-N) in combination with an mRNA vaccine encoding SARS-CoV-2 spike protein(S) (mRNA-S). Chemically modified mRNA-N (pseudouridine) and/or chemically modified mRNA-S (pseudouridine) can be synthesized and packaged in lipid nanoparticles (LNP). In mouse and hamster models, it was shown that mRNA-N alone is immunogenic and can significantly diminish viral loads in the mouse lung after prime-boost intramuscular immunization. In addition, the combinatorial mRNA-N/mRNA-S vaccination induces substantially stronger protection against SARS-CoV-2 than vaccination with mRNA-S alone.

Abstract: In certain aspects the invention provides HIV-1 immunogens, including HIV-1 envelopes with optimized sequences for antibody induction. In some embodiments, the invention provides mRNA sequences of said HIV-1 immunogens.

Abstract: The invention encompasses novel ionizable lipids compounds and their use in lipid nanoparticles delivery systems that are useful in the delivery of nucleic acids to a mammalian subject that can be included for use, for example, as cancer vaccines, gene editing therapeutics, delivery of nucleic acid (e.g., mRNA) encoding antibodies, vaccines for infectious disease, and protein replacement therapeutics. Additionally, the invention encompasses compositions and therapeutics comprising the ionzable lipids in the lipid nanoparticles and the use of the composition and therapeutics for the preparation of a pharmaceutical composition, especially a vaccine, (e.g., for use in the prophylaxis or treatment of infectious diseases, tumor or cancer diseases, rare diseases, allergies, or autoimmune diseases). The invention encompasses methods of treatment or prophylaxis of the aforementioned diseases.

Abstract: In certain aspects the invention provides HIV-1 immunogens, including HIV-1 envelopes with optimized V2 loop for antibody induction.

Abstract: Disclosed herein are methods of increasing the potency of nucleic acid loaded lipid nanoparticles (naLNPs) through certain novel and surprisingly superior LNP manufacturing techniques. Also disclosed are pharmaceutical compositions containing naLNPs manufactured according to the manufacturing methods described herein. The methods disclosed herein overcome major technical difficulties and high costs associated with previous LNP manufacturing techniques. The methods disclosed herein, therefore, greatly improve the industrial production of LNPs in unexpected ways thereby providing more potent naLNPs for nucleic acid delivery. Specifically, the invention disclosed herein are methods that show increased potency naLNPs due to increased mixing concentration of the lipids and mRNA during assembly.

Abstract: Described herein, in some aspects, are bisphosphonate lipid compounds, lipid nanoparticles (LNPs) thereof, and methods of use thereof. In various embodiments, the LNP selectively targets a cell of interest (e.g., a bone cell and/or bone marrow cell, such as a stem cell, stroma cell, osteoblast, osteocyte, osteoclast, bone lining cell, local mesenchymal cell, progenitor cell, mononuclear blood-borne precursor cell, B cell, endothelial cell, granulocytes, T cell, monocytic lineage, B cell lineage, monocytes, cancer cell, tumor cell, tumor cell that metastasizes to bone, blood cancer cell, and multiple myeloma cell, inter alia). In other aspects, the present disclosure relates to methods for in vivo delivery of therapeutic agents to prevent or treat diseases, disorders, or conditions using the LNP compositions of the disclosure.

Abstract: The present application discloses compositions and methods for use of nucleoside modified mRNA that encode for at least one liver regenerative factor. The present invention also relates to compositions and methods for use of nucleoside modified mRNA complexed to nanoparticles. The disclosed compositions and methods are useful for treating acute liver diseases, chronic liver diseases, and/or acetaminophen (acetyl-para-aminophenol, APAP) overdose.

Abstract: The present invention relates to compositions and methods for inducing an adaptive immune response against Hepatitis C virus (HCV) in a subject. In some embodiments, the present invention provides a composition comprising a nucleosidemodified nucleic acid molecule encoding a HCV antigen, adjuvant, or a combination thereof. For example, in some embodiments, the composition comprises a vaccine comprising a nucleoside-modified nucleic acid molecule encoding a HCV antigen, adjuvant, or a combination thereof.

Abstract: The present application discloses compositions and methods for use of nucleoside modified mRNA that encode for at least one liver regenerative factor. The present invention also relates to compositions and methods for use of nucleoside modified mRNA complexed to nanoparticles. The disclosed compositions and methods are useful for treating acute liver diseases, chronic liver diseases, and/or acetaminophen (acetyl-para-aminophenol, APAP) overdose.

Abstract: Immunogenic compositions and methods of their use in eliciting immune responses to coronaviruses, such as SARS-CoV-2 are provided.

Abstract: Disclosed herein is a composition including a nucleoside-modified mRNA encapsulated in a lipid nanoparticle wherein the nucleoside-modified mRNA encodes IL10, IL-6, MIP1a, GDNF (glial cell line-derived neurotrophic factor), or a combination thereof. A method of treated spinal cord injury is also described.