Abstract: Aspects of the disclosure relate to liquid chromatography (e.g., HPLC) methods which enable identification of one or more target nucleic acids in a mixture (e.g., pharmaceutical composition). The disclosure is based, in part, on methods that allow for addition of pharmaceutical compositions (e.g., lipid-based pharmaceutical compositions) directly onto a chromatographic column without the need for first separating target nucleic acids out of the composition. Accordingly, in some embodiments, methods described by the disclosure are useful for assessing the quality of pharmaceutical preparations comprising nucleic acids.

Abstract: Provided herein are methods of reducing adduct formation in lipid nanoparticle compositions comprising a polynucleotide, such as mRNA, and an ionizable lipid; also disclosed are lipid nanoparticle compositions having a reduced adduct content, and methods of detecting the adducts.

Abstract: Aspects of the disclosure relate to liquid chromatography (e.g., HPLC) methods which enable high resolution separations of polynucleotides having hydrophobic portions (e.g., polyadenylated nucleic acids, such as mRNA) based upon the hydrophobic character of the molecules (e.g., polyA tail length). In some embodiments, the disclosure describes liquid chromatographic methods for separating a nucleic acid having a hydrophobic portion (e.g., a polyadenylated nucleic acid, such as an mRNA) from a complex mixture by a mobile phase system that comprises an ion pairing agent selected from Tris, inorganic cations (including e.g., Na, Li, K, ammonium, etc.), biological buffers (e.g., MOPS, HEPES, PIPES, etc.), and other charged or hydrophilic moieties, and lacks conventional ion pairing agents (e.g., Triethylammonium acetate, TEAA). Accordingly, in some embodiments methods described by the disclosure are useful for assessing the quality of pharmaceutical preparations comprising nucleic acids.

Abstract: Provided herein are compositions and methods of reducing adduct formation.

Abstract: Aspects of the disclosure relate to liquid chromatography (e.g., HPLC) methods which enable high resolution separations of polynucleotides of various lengths, sequences, and/or base compositions in a highly tunable manner. In some embodiments, the disclosure describes liquid chromatographic methods for separating a nucleic acid (e.g., a polyadenylated nucleic acid, such as an mRNA) from a complex mixture by using multiple ion pairing agents in the same mobile phase system. Accordingly, in some embodiments methods described by the disclosure are useful for assessing the quality of pharmaceutical preparations comprising nucleic acids.

Abstract: Provided herein are compositions and methods of reducing adduct formation.

Abstract: Provided herein are compositions and methods of reducing adduct formation.

Abstract: Provided herein are compositions and methods of reducing adduct formation.

Abstract: Provided herein are compositions and methods of reducing adduct formation.

Abstract: Aspects of the disclosure relate to liquid chromatography (e.g., HPLC) methods which enable high resolution separations of polynucleotides having hydrophobic portions (e.g., polyadenylated nucleic acids, such as mRNA) based upon the hydrophobic character of the molecules (e.g., polyA tail length). In some embodiments, the disclosure describes liquid chromatographic methods for separating a nucleic acid having a hydrophobic portion (e.g., a polyadenylated nucleic acid, such as an mRNA) from a complex mixture by a mobile phase system that comprises an ion pairing agent selected from Tris, inorganic cations (including e.g., Na, Li, K, ammonium, etc.), biological buffers (e.g., MOPS, HEPES, PIPES, etc.), and other charged or hydrophilic moieties, and lacks conventional ion pairing agents (e.g., Triethylammonium acetate, TEAA). Accordingly, in some embodiments methods described by the disclosure are useful for assessing the quality of pharmaceutical preparations comprising nucleic acids.

Abstract: Aspects of the disclosure relate to liquid chromatography (e.g., HPLC) methods which enable high resolution separations of polynucleotides of various lengths, sequences, and/or base compositions in a highly tunable manner. In some embodiments, the disclosure describes liquid chromatographic methods for separating a nucleic acid (e.g., a polyadenylated nucleic acid, such as an mRNA) from a complex mixture by using multiple ion pairing agents in the same mobile phase system. Accordingly, in some embodiments methods described by the disclosure are useful for assessing the quality of pharmaceutical preparations comprising nucleic acids.