Some aspects of this disclosure provide compositions, methods, and kits for improving the specificity of RNA-programmable endonucleases, such as Cas9. Also provided are variants of Cas9, e.g., Cas9 dimers and fusion proteins, engineered to have improved specificity for cleaving nucleic acid targets. Also provided are compositions, methods, and kits for site-specific nucleic acid modification using Cas9 fusion proteins (e.g., nuclease-inactivated Cas9 fused to a nuclease catalytic domain or a recombinase catalytic domain). Such Cas9 variants are useful in clinical and research settings involving site-specific modification of DNA, for example, genomic modifications.

The invention provides compositions and methods for sequencing nucleic acids and other applications. In sequencing by synthesis, unlabeled reversible terminators are incorporated by a polymerase in each cycle, then labeled after incorporation by binding to the reversible terminator a directly or indirectly labeled antibody or other affinity reagent.

The invention provides compositions and methods for sequencing nucleic acids and other applications. In sequencing by synthesis, unlabeled reversible terminators are incorporated by a polymerase in each cycle, then labeled after incorporation by binding to the reversible terminator a directly or indirectly labeled antibody or other affinity reagent.

The present invention provides a polyethylene glycol-modified endostatin analogue and an application thereof. The endostatin analogue is coupled to polyethylene glycol at lysine away from a nucleolin binding domain, or is coupled to polyethylene glycol at lysine away from a nucleolin binding domain and amidogen at the N end.

The present invention provides a conjugate comprising an albumin binding peptide and a cargo, compositions for directing cargos to the lymphatic system, and vaccines. The methods of the invention can be used to increase an immune response, or to treat cancer or an infectious disease.

The disclosure features novel lipids and compositions involving the same. Lipid nanoparticles (e.g., empty LNPs or loaded LNPs) include a novel lipid as well as additional lipids such as phospholipids, structural lipids, and PEG lipids. Lipid nanoparticles (e.g., empty LNPs or loaded LNPs) further including therapeutic and/or prophylactics such as RNA are useful in the delivery of therapeutic and/or prophylactics to mammalian cells or organs to, for example, regulate polypeptide, protein, or gene expression.

Described herein is the androgen receptor modulator of formula (I)

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in the treatment of prostate cancer in combination with other therapeutic options and in the treatment of diseases or conditions that are amenable to treatment with the androgen receptor modulator, as well as pharmaceutical compositions and medicaments that include such compound.

Described herein is the androgen receptor modulator of formula (I)

##STR00001##

in the treatment of prostate cancer in combination with other therapeutic options and in the treatment of diseases or conditions that are amenable to treatment with the androgen receptor modulator, as well as pharmaceutical compositions and medicaments that include such compound.

This invention relates to a conjugate of formula (I): (A-Z.sup.1-).sub.n-Q-Z.sup.2-D (I), wherein Z.sup.1, Z.sup.2, Q, A, D, and n are as described herein. This invention also relates to a pharmaceutical composition including a pharmaceutically acceptable carrier and a conjugate of formula (I). This invention also relates to a method making a conjugate of formula (I), and the use of the conjugate for treating cancerous conditions, modulating cell membrane microheterogeneity, stimulating an immunoresponse, and forming a network on or near the inner or outer surface of target cells.

This invention relates to a conjugate of formula (I): (A-Z.sup.1-).sub.n-Q-Z.sup.2-D (I), wherein Z.sup.1, Z.sup.2, Q, A, D, and n are as described herein. This invention also relates to a pharmaceutical composition including a pharmaceutically acceptable carrier and a conjugate of formula (I). This invention also relates to a method making a conjugate of formula (I), and the use of the conjugate for treating cancerous conditions, modulating cell membrane microheterogeneity, stimulating an immunoresponse, and forming a network on or near the inner or outer surface of target cells.