The present disclosure generally relates to metal-organic framework nanoparticles containing terminal phosphate-modified oligonucleotides, methods for making the same, and methods of using the same.

Provided is a drug containing a liver targeting specific ligand and a thyroid hormone receptor agonist in its structure, which is a new drug structure formed by linking the liver targeting specific ligand with the thyroid hormone receptor agonist through a branched chain, a linker and a linking chain. Thyroid hormone receptors (TRs) are divided into two subtypes, TR-α and TR-β, wherein, TR-β is mainly expressed in liver, and TR-α is mainly expressed in heart, nervous system, etc. In certain embodiments, it is envisaged that the provided drug has the action of liver targeting, can specifically bring the thyroid hormone receptor agonist into liver, without entering heart and other issues, and may thereby avoid side effects caused by the action of the thyroid hormone receptor agonist on other issues, and maintain its therapeutic efficacy in the treatment of lipid metabolism disorders and related complications.

Provided herein are, inter alia, nucleic acid-peptide conjugates including a non-cell penetrating protein attached at its C-terminus to a phosphorothioate nucleic acid. Attachment of the phosphorothioate nucleic acid to the non-cell penetrating protein conveys stability to and allows for efficient intracellular delivery of the non-cell penetrating peptide. The nucleic acid-peptide conjugates provided herein including embodiments thereof are useful, inter alia, for the treatment of cancer, inflammatory disease, pain, and viral infection.

The disclosure provides peptide products comprising a peptide covalently attached to a surfactant moiety which have improved properties, including increased duration of action and bioavailability. The peptide products are useful for treating insulin resistance, diabetes, obesity, metabolic syndrome and cardiovascular diseases, and conditions associated therewith, such as NASH and PCOS.

Disclosed are nucleic acid nanoparticles, a pharmaceutical composition comprising the same, a drug comprising doxorubicin and a preparation method thereof. The nucleic acid nanoparticles have a nucleic acid structural domain, the nucleic acid structural domain includes a sequence a, a sequence b and a sequence c; the sequence a includes a sequence a1 or a sequence obtained by insertion, deletion or substitution of at least one base in the sequence a1, the sequence b includes a sequence b1 or a sequence obtained by insertion, deletion or substitution of at least one base in the sequence b1 and the sequence c includes a sequence d or a sequence obtained by insertion, deletion or substitution of at least one base in the sequence.

Described are compositions and methods for inhibition of Hepatitis B virus gene expression. RNA interference (RNAi) triggers and RNAi trigger conjugates for inhibiting the expression of Hepatitis B virus gene are described. Pharmaceutical compositions comprising one or more HBV RNAi triggers optionally with one or more additional therapeutics are also described. Delivery of the described HBV RNAi triggers to infected liver in vivo provides for inhibition of HBV gene expression and treatment.

The invention provides novel compounds and polymers, degradable hydrogel compositions, medical devices and implants, as well as methods thereof, that allow on-demand release and controlled delivery of antimicrobial agents.

The present invention provides refillable drug delivery systems, as well as methods of refilling the systems, and methods of using them to treat diseases.

A mutant SaCas9 protein such as a protein having an amino acid sequence resulting from mutations of glutamic acid at the 782-position to lysine (E782K), leucine at the 800-position to arginine (L800R), asparagine at the 968-position to arginine (N968R), asparagine at the 985-position to alanine (N985A), arginine at the 991-position to alanine (R991A), alanine at the 1021-position to serine (A1021S), threonine at the 927-position to lysine (T927K), lysine at the 929-position to asparagine (K929N), and isoleucine at the 1017-position to phenylalanine (I1017F) in SEQ ID NO: 2 has relaxed restriction on target sequence while maintaining binding ability to guide RNA, and is useful as a tool for gene editing.

Provided are a siRNA for inhibiting the expression of hepatitis B virus gene, and a pharmaceutical composition and conjugate containing the siRNA. Each nucleotide in the siRNA is independently a modified nucleotide. The siRNA comprises a sense strand and an antisense strand. The sense strand of the siRNA comprises a nucleotide sequence 1 having the same length and no more than three nucleotides different from the nucleotide sequence shown in SEQ ID NO: 155, and the antisense strand of the siRNA comprises a nucleotide sequence 2 having the same length and no more than three nucleotides different from the nucleotide sequence shown in SEQ ID NO: 156.