Abstract: The disclosure provides methods and compositions for delivering RNA constructs to cells for functional expression and/or activity. In some aspects, the disclosure provides a composition comprising a multi-functionalized nanoparticle. The multi-functionalized nanoparticles comprise a core functionalized with at least one RNA molecule, at least one cell penetrating peptide (CPP), and at least one positively charged moiety, each of which is independently attached to the core, optionally with linker moieties. In some embodiments, the RNA molecule is an uncapped mRNA molecule with the 5? end attached to a linker moiety that is attached to the core. The multi-functionalized nanoparticle is substantially neutral, negatively or positively charged.

Abstract: Provided are functionalized nanoparticles for penetrating through a mammalian cell membrane and delivering intracellularly one or more biologically active molecules comprising a nanoparticle core, one or more cell membrane-penetrating molecule(s), and one or more biologically active molecule(s) for introducing or affecting one or more cellular function(s). functionalized nanoparticles. Also provided are methods for making functionalized nanoparticles and methods for using functionalized nanoparticles, including methods for treating diseases and disorders, inducing the reprograming of cells, and for gene editing.

Abstract: This disclosure relates to compositions and methods for editing or altering target nucleotide sequences based on nanoparticle delivery vehicles. The compositions and methods can be applied to influence the functional expression of target gene products encoded by DNA and/or RNA. In some embodiments, the altered gene sequences are useful to normalize and regulate the function of target cells.

Abstract: This disclosure relates to compositions and methods for reprogramming an initial cell (e.g., somatic cell) to generate specialized cell types of interest, such as cardiac, hepatic, blood, neuronal and other cells from human somatic cells. In some embodiments, initial (e.g., somatic) cell is a human cell thus producing human induced cell types of interest. In some embodiments, the compositions and methods incorporate nanoparticles functionalized with biologically active molecules (RNAs, proteins, peptides and other small molecules). These newly generated (i.e., “induced”) specialized cells are useful to improve organ function and/or tissue regeneration (heart, liver, etc.) and to screen drugs for functional activity.

Abstract: Provided are functionalized nanoparticles for penetrating through a mammalian cell membrane and delivering intracellularly one or more biologically active molecules comprising a nanoparticle core, one or more cell membrane-penetrating molecule(s), and one or more biologically active molecule(s) for introducing or affecting one or more cellular function(s). functionalized nanoparticles. Also provided are methods for making functionalized nanoparticles and methods for using functionalized nanoparticles, including methods for treating diseases and disorders, inducing the reprogramming of cells, and for gene editing.

Abstract: Functionalized biocompatible nanoparticles capable of penetrating through a mammalian cell membrane and delivering intracellularly a plurality of bioactive molecules for modulating a cellular function are disclosed herein The functionalized biocompatible nanoparticles comprise: a central nanoparticle ranging in size from about 5 to about 50 nm and having a polymer coating thereon, a plurality of functional groups covalently attached to the polymer coating, wherein the plurality of bioactive molecules are attached to the plurality of the functional groups, and wherein the plurality of bioactive molecules include at least a peptide and a protein, and wherein the peptide is capable of penetrating through the mammalian cell membrane and entering into the cell, and wherein the protein is capable of providing a new functionality within the cell. The protein may be a transcription factor selected from the group consisting of Oct4, Sox2, Nanog, Lin28, cMyc, and Klf4.

Abstract: Functionalized biocompatible nanoparticles capable of penetrating through a mammalian cell membrane and delivering intracellularly a plurality of bioactive molecules for modulating a cellular function are disclosed herein The functionalized biocompatible nanoparticles comprise: a central nanoparticle ranging in size from about 5 to about 50 nm and having a polymer coating thereon, a plurality of functional groups covalently attached to the polymer coating, wherein the plurality of bioactive molecules are attached to the plurality of the functional groups, and wherein the plurality of bioactive molecules include at least a peptide and a protein, and wherein the peptide is capable of penetrating through the mammalian cell membrane and entering into the cell, and wherein the protein is capable of providing a new functionality within the cell. The protein may be a transcription factor selected from the group consisting of Oct4, Sox2, Nanog, Lin28, cMyc, and Klf4.

Abstract: The invention is directed to a method of treating severe neutropenia, and in particular, cyclic neutropenia (CN) or severe congenital neutropenia (SCN), in a patient in need of such treatment comprising: administering a therapeutically effective amount of a compound of Formula (I) or a pharmaceutically acceptable salt thereof.

Abstract: The invention is directed to a method of treating severe neutropenia, and in particular, cyclic neutropenia (CN) or severe congenital neutropenia (SCN), in a patient in need of such treatment comprising: administering a therapeutically effective amount of a compound of Formula (I) or a pharmaceutically acceptable salt thereof.