The invention provides compositions including stabilized multilamellar lipid vesicles having crosslinked lipid bilayers (referred to herein as interbilayer-crosslinked multilamellar vesicles or ICMV) and including an ALK variant, pharmaceutical compositions containing vesicles (e.g., ICMV) including an ALK variant, and methods of treatment using such compositions. The invention provides compositions including stabilized multilamellar lipid vesicles with crosslinked lipid bilayers (e.g., an interbilayer-crosslinked multilamellar vesicle or ICMV) containing an Anaplastic lymphoma kinase (ALK) variant as an antigen that is associated with solid tumor cancers.

The invention provides compositions including stabilized multilamellar lipid vesicles having crosslinked lipid bilayers (referred to herein as interbilayer-crosslinked multilamellar vesicles or ICMV) and including an ALK variant, pharmaceutical compositions containing vesicles (e.g., ICMV) including an ALK variant, and methods of treatment using such compositions. The invention provides compositions including stabilized multilamellar lipid vesicles with crosslinked lipid bilayers (e.g., an interbilayer-crosslinked multilamellar vesicle or ICMV) containing an Anaplastic lymphoma kinase (ALK) variant as an antigen that is associated with solid tumor cancers.

The present invention relates generally to a population of cells genetically modified to produce insulin in a glucose responsive manner and uses thereof. More particularly, the present invention relates to a population of cells genetically modified to produce insulin in response to physiologically relevant levels of glucose and uses thereof. The cells of the present invention are useful in a wide variety of applications, in particular in the context of therapeutic and prophylactic regimes directed to the treatment of diabetes and/or the amelioration of symptoms associated with diabetes, based on the transplantation of the cells of the present invention into mammals requiring treatment. Also facilitated is the design of in vitro based screening systems for testing the therapeutic effectiveness and/or toxicity of potential adjunctive treatment regimes.

The present invention relates generally to a population of cells genetically modified to produce insulin in a glucose responsive manner and uses thereof. More particularly, the present invention relates to a population of cells genetically modified to produce insulin in response to physiologically relevant levels of glucose and uses thereof. The cells of the present invention are useful in a wide variety of applications, in particular in the context of therapeutic and prophylactic regimes directed to the treatment of diabetes and/or the amelioration of symptoms associated with diabetes, based on the transplantation of the cells of the present invention into mammals requiring treatment. Also facilitated is the design of in vitro based screening systems for testing the therapeutic effectiveness and/or toxicity of potential adjunctive treatment regimes.

Disclosed herein are novel compounds, pharmaceutical compositions comprising such compounds and related methods of their use. The compounds described herein are useful, e.g., as liposomal delivery vehicles to facilitate the delivery of encapsulated polynucleotides to target cells and subsequent iransfection of said target cells, and in certain embodiments are characterized as having one or more properties that afford such compounds advantages relative to other similarly classified lipids.

Disclosed herein are novel compounds, pharmaceutical compositions comprising such compounds and related methods of their use. The compounds described herein are useful, e.g., as liposomal delivery vehicles to facilitate the delivery of encapsulated polynucleotides to target cells and subsequent iransfection of said target cells, and in certain embodiments are characterized as having one or more properties that afford such compounds advantages relative to other similarly classified lipids.

The present invention includes methods and compositions for increasing longevity of a cell and increasing cellular resistance to stress. In certain embodiments, the invention includes a method to induce gene expression of a homolog of Pachytene Checkpoint 2 (pch-2) or bmk-1 gene. The present invention also includes methods to treat oxidative stress or induce cellular death or apoptosis by administering a composition comprising a modulator of pch-2 or bmk-1 homolog gene expression.

The present invention includes methods and compositions for increasing longevity of a cell and increasing cellular resistance to stress. In certain embodiments, the invention includes a method to induce gene expression of a homolog of Pachytene Checkpoint 2 (pch-2) or bmk-1 gene. The present invention also includes methods to treat oxidative stress or induce cellular death or apoptosis by administering a composition comprising a modulator of pch-2 or bmk-1 homolog gene expression.

The present invention provides, among other things, methods of treating ornithine transcarbamylase (OTC) deficiency, including administering to a subject in need of treatment a composition comprising an mRNA encoding an ornithine transcarbamylase (OTC) protein at an effective dose and an administration interval such that at least one symptom or feature of the OTC deficiency is reduced in intensity, severity, or frequency or has delayed onset. In some embodiments, the mRNA is encapsulated in a liposome comprising one or more cationic lipids, one or more non-cationic lipids, one or more cholesterol-based lipids and one or more PEG-modified lipids.

The present invention provides, among other things, methods of treating ornithine transcarbamylase (OTC) deficiency, including administering to a subject in need of treatment a composition comprising an mRNA encoding an ornithine transcarbamylase (OTC) protein at an effective dose and an administration interval such that at least one symptom or feature of the OTC deficiency is reduced in intensity, severity, or frequency or has delayed onset. In some embodiments, the mRNA is encapsulated in a liposome comprising one or more cationic lipids, one or more non-cationic lipids, one or more cholesterol-based lipids and one or more PEG-modified lipids.