Provided herein are placental stem cells that exhibit increased survival (“enhanced placental stem cells”), compositions comprising such placental stem cells, and methods of using such placental stem cells and compositions.

Disclosed herein are compositions and methods for cellular reprogramming. The compositions comprise one or more miRs and an activator of NFκB. Also provided are methods for enhancing or upregulating cardiomyocyte maturation in a cell or a subject and methods for inhibiting or downregulating cardiomyocyte maturation.

RNAs, such as miRNA and siRNA, and their use in treating complement-mediated disorders, are described.

The present invention relates to a method for inducing megakaryocytic differentiation of hematopoietic stem/progenitor cells (HSPCs). The method comprises transferring into the HSPCs an effective amount of small RNAs. The HSPCs may differentiate into megakaryocytes in the absence of thrombopoietin (TPO) and/or without using megakaryocytic microparticles (MkMPs). The small RNAs may be micro RNAs (miRs) selected from the group consisting of miR-486, miR-22, miR-191, miR-181, miR-378, miR-26, let-7, miR-92, miR-126, miR-92, miR-21, miR-146, miR-181, and combinations thereof. For example, the small RNAs are miR-486 and miR-22. The small RNAs may be synthetic or isolated from cells. Also provided is a method for enhancing megakaryocytic differentiation of HSPCs cultured with megakaryocytic microparticles MkMPs in the presence of an effective amount of one or more exogenous small RNAs (e.g., miR-486).

The present invention relates to a method for inducing megakaryocytic differentiation of hematopoietic stem/progenitor cells (HSPCs). The method comprises transferring into the HSPCs an effective amount of small RNAs. The HSPCs may differentiate into megakaryocytes in the absence of thrombopoietin (TPO) and/or without using megakaryocytic microparticles (MkMPs). The small RNAs may be micro RNAs (miRs) selected from the group consisting of miR-486, miR-22, miR-191, miR-181, miR-378, miR-26, let-7, miR-92, miR-126, miR-92, miR-21, miR-146, miR-181, and combinations thereof. For example, the small RNAs are miR-486 and miR-22. The small RNAs may be synthetic or isolated from cells. Also provided is a method for enhancing megakaryocytic differentiation of HSPCs cultured with megakaryocytic microparticles MkMPs in the presence of an effective amount of one or more exogenous small RNAs (e.g., miR-486).

Disclosed herein are compositions and methods for targeted treatment of liver cancers with Paclitaxel and miR-122. The disclosed composition comprises RNA nanostructure conjugated to a hepatocyte targeting ligand, paclitaxel, and miR-122 for use in intracellular drug delivery to liver cancer cells. The RNA nanoparticle can involve three or more self-assembled synthetic RNA oligonucleotides that form a central core domain and at least three double-stranded arms arranged around the core domain and extending away from the central core domain.

Disclosed herein is a modified ribonucleotide comprising a nucleoside comprising N4-acetylcytidine and/or 5-hydroxymethyluridine, and polyribonucleotides comprising the same. Also provided herein are compositions comprising a polyribonucleotide of the present disclosure and methods of making and using the same.

The disclosed systems and methods are configurable central nervous system (CNS) delivery solutions for therapeutics, such as genetic medicines. The systems and methods first infuse a therapeutic bolus within intrathecal space and subsequently infuse a flush fluid to move the therapeutic bolus rostrally toward a target area and achieve a desired spread in the spine and/or brain. The second location can be at a location caudal to the delivery location of the therapeutic bolus.

The disclosure features methods of reducing or inhibiting an anti-drug antibody response in a subject, as well as methods of reducing or inhibiting unwanted immune cell activation in a subject to be treated with a messenger RNA (mRNA), comprising administering to the subject a mRNA, e.g., a chemically modified messenger RNA (mmRNA), encoding a polypeptide of interest, wherein the mRNA comprises at least one microRNA (miR) binding site for a miR expressed in immune cells, such as miR-126 binding site and/or miR-142 binding site, such that an anti-drug antibody response to the polypeptide or interest, or unwanted immune cell activation (e.g., B cell activation, cytokine secretion), is reduced or inhibited in the subject. The disclosure further provides therapeutic treatment regimens designed to reduce or inhibit ADA or unwanted immune cell activation (e.g., B cell activation, cytokine secretion) in a subject being treated with mRNA-based therapeutics.

In one aspect, the invention relates to a method of loading exosomes with oligonucleotide cargo, by incubating an oligonucleotide comprising one or more hydrophobic modifications with a population of exosomes for a period of time sufficient to allow loading of the exosomes with the oligonucleotide. Exosomes loaded with hydrophobically modified oligonucleotide cargo, and uses thereof, are also provided.