The present invention provides, a cationic lipid represented by the formula (1) (wherein each symbol is as defined in the specification), a lipid membrane structure using the aforementioned cationic lipid, a nucleic acid-introducing agent using the aforementioned cationic lipid, and a method for introducing a nucleic acid by using the aforementioned nucleic acid-introducing agent.

##STR00001##

The disclosure features novel lipids and compositions involving the same. Lipid nanoparticles (e.g., empty LNPs or loaded LNPs) include a novel lipid as well as additional lipids such as phospholipids, structural lipids, and PEG lipids. Lipid nanoparticles (e.g., empty LNPs or loaded LNPs) further including therapeutic and/or prophylactics such as RNA are useful in the delivery of therapeutic and/or prophylactics to mammalian cells or organs to, for example, regulate polypeptide, protein, or gene expression.

Disclosed herein are compositions and pharmaceutical formulations that comprise a binding moiety conjugated to a polynucleic acid molecule and a polymer. Also described herein include methods for treating a cancer which utilize a composition or a pharmaceutical formulation comprising a binding moiety conjugated to a polynucleic acid molecule and a polymer.

Disclosed are formulations for providing a therapeutic bioactive polypeptide to injured tissue. Formulations include mineral coated microparticles wherein a polynucleotide is adsorbed to the mineral layer. Other formulations include a carrier including mineral coated microparticles wherein mineral coated microparticles include a polynucleotide. Also disclosed are methods for sustained delivery of a bioactive polypeptide and methods for treating chronic wounds using a formulation for providing sustained delivery of the bioactive peptide.

Disclosed herein are compositions and methods related to megakaryocyte-derived extracellular vesicles derived from human pluripotent stem cells, where the megakaryocyte-derived extracellular vesicles may be utilized for drug delivery and treating various diseases.

The invention relates to mRNA therapy for the treatment of Acute Intermittent Porphyria (AIP). mRNAs for use in the invention, when administered in vivo, encode human porphobilinogen deaminase (PBGD), isoforms thereof, functional fragments thereof, and fusion proteins comprising PBGD. mRNAs of the invention are preferably encapsulated in lipid nanoparticles (LNPs) to affect efficient delivery to cells and/or tissues in subjects, when administered thereto. mRNA therapies of the invention increase and/or restore deficient levels of PBGD expression and/or activity in subjects. mRNA therapies of the invention further decrease levels of toxic metabolites associated with deficient PBGD activity in subjects, namely porphobilinogen and aminolevulinate (PBG and ALA).

The disclosure features lipid nanoparticle (LNP) compositions comprising immune checkpoint inhibitor molecules and uses thereof. The LNP compositions of the present disclosure comprise mRNA therapeutics encoding immune checkpoint inhibitor polypeptides, e.g., PD-L1, PD-L2, B7-H3, B7-H4, CD200 Galectin 9 and CTLA4. The LNP compositions of the present disclosure can reprogram dendritic cells, suppress T cells and/or induce immune tolerance in vivo.

This disclosure relates to the field of RNA to prevent or treat coronavirus infection. In particular, the present disclosure relates to methods and agents for vaccination against coronavirus infection and inducing effective coronavirus antigen-specific immune responses such as antibody and/or T cell responses. Specifically, in one embodiment, the present disclosure relates to methods comprising administering to a subject RNA encoding a peptide or protein comprising an epitope of SARS-CoV-2 spike protein (S protein) for inducing an immune response against coronavirus S protein, in particular S protein of SARS-CoV-2, in the subject, i.e., vaccine RNA encoding vaccine antigen.

The present application is directed to cargo delivery complexes for intracellular delivery of a cargo molecule comprising: a first peptide comprising a cell-penetrating peptide (CPP), a second peptide comprising a cell-penetrating peptide, and a cargo molecule. The second peptide comprises a polyethylene glycol (PEG) moiety linked to the second CPP, and the first peptide does not have a PEG moiety. The present application is also directed to a cargo delivery complex comprising a CPP and a cargo molecule wherein the CPP is a retro-inverso peptide. The present application is also directed to a cargo delivery complex comprising a CPP and a cargo molecule wherein the peptide further comprises a targeting sequence selected from the group consisting of GYVSK, GYVS, YIGS and YIGSR. Methods of making and using the cargo delivery complexes are also disclosed.

Compounds are provided having the following structure: ##STR00001##
or a pharmaceutically acceptable salt, tautomer or stereoisomer thereof, wherein R.sup.1, R.sup.2, R.sup.3, L.sup.1, L.sup.2, G.sup.1, G.sup.2 and G.sup.3 are as defined herein. Use of the compounds as a component of lipid nanoparticle formulations for delivery of a therapeutic agent, compositions comprising the compounds and methods for their use and preparation are also provided.