In alternative embodiments, the invention provides methods for treating, ameliorating or protecting (preventing) an individual or a patient against a disease, an infection or a condition responsive to an increased paracrine polypeptide level in vivo comprising: providing a paracrine polypeptide-encoding nucleic acid or gene operatively linked to a transcriptional regulatory sequence; or an expression vehicle, a vector, a recombinant virus, or equivalent, having contained therein a paracrine-encoding nucleic acid or gene, and the expression vehicle, vector, recombinant virus, or equivalent can express the paracrine-encoding nucleic acid or gene in a cell or in vivo; and administering or delivering the paracrine polypeptide-encoding nucleic acid or gene operatively linked to a transcriptional regulatory sequence, or the expression vehicle, vector, recombinant virus, or equivalent, to an individual or a patient in need thereof, thereby treating, ameliorating or protecting (preventing) the individual or patient against the disease, infection or condition responsive to an increased paracrine polypeptide level.

Disclosed are cationic lipids which are compounds of Formula I. Cationic lipids provided herein can be useful for delivery and expression of mRNA and encoded protein, e.g., as a component of liposomal delivery vehicle, and accordingly can be useful for treating various diseases, disorders and conditions, such as those associated with deficiency of one or more proteins. ##STR00001##

Disclosed are cationic lipids which are compounds of Formula I. Cationic lipids provided herein can be useful for delivery and expression of mRNA and encoded protein, e.g., as a component of liposomal delivery vehicle, and accordingly can be useful for treating various diseases, disorders and conditions, such as those associated with deficiency of one or more proteins. ##STR00001##

The disclosure relates to polynucleotides comprising an open reading frame of linked nucleosides encoding human methylmalonyl-CoA mutase precursor, human methylmalonyl-CoA mutase (MCM) mature form, or functional fragments thereof. In some embodiments, the disclosure includes methods of treating methylmalonic acidemia in a subject in need thereof comprising administering an mRNA encoding an MCM polypeptide.

The disclosure relates to polynucleotides comprising an open reading frame of linked nucleosides encoding human methylmalonyl-CoA mutase precursor, human methylmalonyl-CoA mutase (MCM) mature form, or functional fragments thereof. In some embodiments, the disclosure includes methods of treating methylmalonic acidemia in a subject in need thereof comprising administering an mRNA encoding an MCM polypeptide.

Disclosed are cationic lipids which are compounds of Formula (A). Cationic lipids provided herein can be useful for delivery and expression of mRNA and encoded protein, e.g., as a component of liposomal delivery vehicle, and accordingly can be useful for treating various diseases, disorders and conditions, such as those associated with deficiency of one or more proteins.

##STR00001##

Disclosed are cationic lipids which are compounds of Formula (A). Cationic lipids provided herein can be useful for delivery and expression of mRNA and encoded protein, e.g., as a component of liposomal delivery vehicle, and accordingly can be useful for treating various diseases, disorders and conditions, such as those associated with deficiency of one or more proteins.

##STR00001##

In alternative embodiments, provided are methods for increasing levels of and/or upregulating the expression of ApoA-I Binding Protein (APOA1BP, AIBP, or AI-BP) to treat, ameliorate, prevent, reverse, decrease the severity or duration of: a neuropathic pain, including an inflammation-induced neuropathic pain, a nerve or CNS inflammation, a, a post nerve injury pain, a post-surgical pain, a chemotherapeutic-induced peripheral neuropathy (CIPN) (e.g., cisplatin-induced allodynia) a neurodegeneration or neurodegenerative disease or condition, a migraine, and/or a hyperalgesia. In alternative embodiments, provided are methods comprising administering formulations and pharmaceutical compositions comprising an APOA1BP polypeptide or protein that is a human or a mammalian APOA1BP, or an AIBP1 or an AIBP2, or a recombinant, peptidomimetic or a synthetic APOA1BP, or a bioisostere of an ApoA-I Binding Protein to treat, ameliorate prevent, reverse, decrease the severity of a neuropathic pain, a TLR4-mediated allodynia and/or a hyperalgesia.

In alternative embodiments, provided are methods for increasing levels of and/or upregulating the expression of ApoA-I Binding Protein (APOA1BP, AIBP, or AI-BP) to treat, ameliorate, prevent, reverse, decrease the severity or duration of: a neuropathic pain, including an inflammation-induced neuropathic pain, a nerve or CNS inflammation, a, a post nerve injury pain, a post-surgical pain, a chemotherapeutic-induced peripheral neuropathy (CIPN) (e.g., cisplatin-induced allodynia) a neurodegeneration or neurodegenerative disease or condition, a migraine, and/or a hyperalgesia. In alternative embodiments, provided are methods comprising administering formulations and pharmaceutical compositions comprising an APOA1BP polypeptide or protein that is a human or a mammalian APOA1BP, or an AIBP1 or an AIBP2, or a recombinant, peptidomimetic or a synthetic APOA1BP, or a bioisostere of an ApoA-I Binding Protein to treat, ameliorate prevent, reverse, decrease the severity of a neuropathic pain, a TLR4-mediated allodynia and/or a hyperalgesia.

Disclosed herein is a method for inhibiting or preventing Vibrio cholera toxin production in a subject, the method comprising enterally administering to the subject a pharmaceutically effective amount of a fatty acid dissolved or suspended in a pharmaceutically acceptable carrier, wherein the fatty acid contains 10 to 30 carbon atoms, such as an unsaturated fatty acid such as a cis-2-unsaturated fatty acid, such as a fatty acid having the formula:

##STR00001##

wherein n is an integer of 6-26, and the fatty acid optionally includes a second carbon-carbon double bond resulting from removal of two hydrogen atoms on adjacent carbon atoms. Also disclosed herein is a method for treating or preventing a Vibrio infection comprising administering to a subject in need of treatment an effective amount of a genetically engineered bacterium, wherein the genetically engineered bacterium comprises an exogenous nucleic acid encoding an enzyme that produces a diffusible signal factor (DSF) by introducing a cis-2 double bond to a fatty acid.