The disclosure provides ionizable amine lipids and salts thereof (e.g., pharmaceutically acceptable salts thereof) useful for the delivery of biologically active agents, for example delivering biologically active agents to cells to prepare engineered cells. The ionizable amine lipids disclosed herein are useful as ionizable lipids in the formulation of lipid nanoparticle-based compositions.

The disclosure provides ionizable amine lipids and salts thereof (e.g., pharmaceutically acceptable salts thereof) useful for the delivery of biologically active agents, for example delivering biologically active agents to cells to prepare engineered cells. The ionizable amine lipids disclosed herein are useful as ionizable lipids in the formulation of lipid nanoparticle-based compositions.

Provide herein are compounds and pharmaceutical compositions suitable as modulators of hemoglobin, methods and intermediates for their preparation, and methods for their use in treating disorders mediated by hemoglobin and disorders that would benefit from tissue and/or cellular oxygenation.

The present document describes compounds, or pharmaceutically acceptable salt thereof, of a core formula (I) where R.sub.1 features an amine group, particularly useful in the formulation of lipid particles including nucleic acid therapeutic agents, or proteins, or both, and for delivery of nucleic acid and protein therapeutics to cells in vivo or ex vivo, including anticancer and vaccine applications.

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The present document describes compounds, or pharmaceutically acceptable salt thereof, of a core formula (I) where R.sub.1 features an amine group, particularly useful in the formulation of lipid particles including nucleic acid therapeutic agents, or proteins, or both, and for delivery of nucleic acid and protein therapeutics to cells in vivo or ex vivo, including anticancer and vaccine applications.

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The present invention relates to novel linkers containing a 2,3-disubstituted succinic group, or 2-monosubstituted, or 2,3-disubstituted fumaric or maleic (trans (E)- or cis (Z)-butenedioic), or acetylenedicarboxyl group for conjugation of a cytotoxic agent, and/or one or more different functional molecules per linker to a cell-binding molecule, through bridge linking pairs of thiols on the cell-binding molecule specifically. The invention also relates to methods of making such linkers, and of using such linkers in making homogeneous conjugates, as well as of application of the conjugates in treatment of cancers, infections and autoimmune disorders.

The present disclosure relates to compounds, compositions and methods for inhibiting choline metabolism, e.g., conversion of choline to trimethylamine. Disclosed herein are compounds, compositions, and methods for inhibiting choline metabolism, e.g., conversion of choline to TMA. Also disclosed herein are compounds, methods and compositions for inhibiting choline metabolism by gut microbiota resulting in reduction in the formation of trimethylamine (TMA) and trimethylamine N-oxide (TMAO).

Methods described herein enable the production of numerous molecular species through decarboxylative cross-coupling via use of photoredox and transition metal catalysts. For example, methods described herein enable the production of numerous molecular species through decarboxylative cross-coupling via use of photoredox and transition metal catalysts. A method described herein, in some embodiments, comprises providing a reaction mixture including a photoredox catalyst, a transition metal catalyst, a coupling partner and a substrate having a carboxyl group. The reaction mixture is irradiated with a radiation source resulting in cross-coupling of the substrate and coupling partner via a mechanism including decarboxylation, wherein the coupling partner is selected from the group consisting of a substituted aromatic compound and a substituted aliphatic compound.

Methods described herein enable the production of numerous molecular species through decarboxylative cross-coupling via use of photoredox and transition metal catalysts. For example, methods described herein enable the production of numerous molecular species through decarboxylative cross-coupling via use of photoredox and transition metal catalysts. A method described herein, in some embodiments, comprises providing a reaction mixture including a photoredox catalyst, a transition metal catalyst, a coupling partner and a substrate having a carboxyl group. The reaction mixture is irradiated with a radiation source resulting in cross-coupling of the substrate and coupling partner via a mechanism including decarboxylation, wherein the coupling partner is selected from the group consisting of a substituted aromatic compound and a substituted aliphatic compound.

Provided herein are ionizable lipids represented by the Formula (I): or a pharmaceutically acceptable salt thereof, wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.1′, R.sup.2′, R.sup.3′, R.sup.4′, R.sup.5′, R.sup.6′, m, and n are as defined herein. Also provided herein are lipid nanoparticle (LNP) compositions comprising an ionizable lipid of the invention and a capsid-free, non-viral vector (e.g., ceDNA). These LNPs can be used to deliver a capsid-free, non-viral DNA vector to a target site of interest (e.g., cell, tissue, organ, and the like).

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