The present embodiment provides a compound represented by the formula (1):

Q-CHR.sub.2  (1)

(Q is a nitrogen-containing aliphatic group containing two or more tertiary nitrogens but no oxygen, and R is an aliphatic group containing a biodegradable group). From the compound in combination with other lipids such as a lipid capable of reducing aggregation, lipid particles can be formed. Further, the compound can be used for a pharmaceutical composition to deliver an activator into cells.

Disclosed herein are non-naturally occurring vesicle comprising a chimeric vesicle localization moiety comprising a surface-and-transmembrane domain of a first vesicle localization moiety and a cytosolic domain of a second vesicle localization moiety, the method of making said vesicle and uses thereof.

Provided herein are compositions comprising a liposome comprising ribonucleic acid (RNA) molecules and a cationic lipid, wherein the RNA molecules bind to or encode an epitope of a nucleic acid encoding a fusion protein expressed by a tumor. The disclosure also provides a nanoparticle comprising a positively-charged surface and an interior comprising (i) a core and (ii) at least two nucleic acid layers, wherein each nucleic acid layer is positioned between a cationic lipid bilayer, and nucleic acid molecules in the nucleic acid layers comprise a sequence of a nucleic acid molecule expressed by slow-cycling cells (SCCs). Also provided herein re methods of making a nanoparticle and methods of increasing an immune response against a tumor in a subject. Methods of treating a subject with a disease are provided herein.

Disclosed are lipid compounds comprising imidazole heads and lipidoid nanoparticles (LNPs) comprising the lipidoid compounds disclosed herein for efficient nucleic acid delivery to T cells.

The present invention relates to a cationic lipid having one or more biodegradable groups located in a lipidic moiety (e.g., a hydrophobic chain) of the cationic lipid. These cationic lipids may be incorporated into a lipid particle for delivering an active agent, such as a nucleic acid. The invention also relates to lipid particles comprising a neutral lipid, a lipid capable of reducing aggregation, a cationic lipid of the present invention, and optionally, a sterol. The lipid particle may further include a therapeutic agent such as a nucleic acid.

The present invention provides a hybrid biocompatible carrier (hybridosome) which comprises structural and bioactive elements originating from at least one biocompatible delivery module (BDM) and at least one engineered drug encapsulation module (EDEM) comprising at least one tunable fusogenic moiety. The invention further provides pharmaceutical compositions comprising said hybridosomes, processes for their manufacture, as well as pharmaceutical uses and pharmaceutical methods based thereon.

Half of the cancers typically occur due to ineffective capability in their p53 proteins. The invention supplies the cells of the human body or patient with mRNA which will generate effective wild-type p53 proteins, so that this said protein can conduct proper surveillance inside the body's cells and act to destroy cells which have become or are about to become cancerous. The invention also includes introduction of interfering RNA to degrade mutated p53, allowing wild-type p53 proteins to form functional oligomers for cellular surveillance.

The present invention provides, among other things, methods of delivering mRNA in vivo, including administering to a subject in need of delivery a composition comprising an mRNA encoding a protein, encapsulated within a liposome such that the administering of the composition results in the expression of the protein encoded by the mRNA in vivo, wherein the liposome comprises a cationic lipid of formula I-c:

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or a pharmaceutically acceptable salt thereof.

The present invention provides, among other things, methods and compositions of formulating nucleic acid-containing nanoparticles for efficient delivery of payload in vivo such that the method and compositions can be used to generate mRNA vaccines.

Provided is a liposomal sustained-release composition for use in treatment of pulmonary disease. The liposomal sustained release composition comprises a liposome that includes a polyethylene glycol (PEG)-modified lipid and encapsulates a tyrosine kinase inhibitor. Tyrosine kinase inhibitor is stably entrapped in the liposome, and the resulting liposomal drug formulation can be aerosolized or nebulized for administration via inhalation. This aerosolized liposomal drug formulation yields consistent pharmacokinetic and pharmacodynamic profiles while achieving desired efficacy and safety.