Provided are nucleotide sequences encoding polypeptides with ribonuclease III activity, wherein the nucleotide sequences have been modified to reduce their regulation by miRNAs. In some embodiments, the nucleotide sequences are at least 50% and as much as 100% identical to SEQ ID NO: 20 or SEQ ID NO: 22, and/or encode polypeptides that are at least 90% percent identical to SEQ ID NO: 23. Also provided are vectors and host cells that include the nucleotide sequences, methods for expressing the nucleotide sequences in cells, tissues, and organs, which in some embodiments can be in the eye of a subject in need thereof, methods for preventing and/or treating development of diseases or disorders and/or for restoring undesirably low DICER1 expression using the nucleotide sequences, and pharmaceutical compositions that have the presently disclosed nucleotide sequences.

Provided are nucleotide sequences encoding polypeptides with ribonuclease III activity, wherein the nucleotide sequences have been modified to reduce their regulation by miRNAs. In some embodiments, the nucleotide sequences are at least 50% and as much as 100% identical to SEQ ID NO: 20 or SEQ ID NO: 22, and/or encode polypeptides that are at least 90% percent identical to SEQ ID NO: 23. Also provided are vectors and host cells that include the nucleotide sequences, methods for expressing the nucleotide sequences in cells, tissues, and organs, which in some embodiments can be in the eye of a subject in need thereof, methods for preventing and/or treating development of diseases or disorders and/or for restoring undesirably low DICER1 expression using the nucleotide sequences, and pharmaceutical compositions that have the presently disclosed nucleotide sequences.

This disclosure relates to the field of exosome delivery systems. In particular, compositions comprising adipose-derived exosomes that may be used as a delivery system are encompassed. The exosome delivery system can be used to deliver exogenous cargo such as miRNA and other inhibitory RNAs, as well as proteins, to target cells in a subject.

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).

The disclosure features mRNAs engineered with one or more microRNA binding sites targeted by a microRNA(s) that are differentially expressed in a target immune cell relative to a plurality of non-target immune cells. The disclosure also features methods of using the same, for example, for selectively degrading the mRNA in the target immune cell relative to the plurality of non-target immune cells.

The disclosure features mRNAs engineered with one or more microRNA binding sites targeted by a microRNA(s) that are differentially expressed in a target immune cell relative to a plurality of non-target immune cells. The disclosure also features methods of using the same, for example, for selectively degrading the mRNA in the target immune cell relative to the plurality of non-target immune cells.

This disclosure provides a CRISPR-Cas system with both RNase and Dnase activity for genetic editing and methods of use thereof. The disclosed CRISPR-Cas system can function in a cell-specific manner, which enables in vivo editing while mitigating the risk of off-target effects.

This disclosure provides a CRISPR-Cas system with both RNase and Dnase activity for genetic editing and methods of use thereof. The disclosed CRISPR-Cas system can function in a cell-specific manner, which enables in vivo editing while mitigating the risk of off-target effects.

The present invention includes methods for detecting cancer in a subject and measuring the effectiveness of a cancer treatment. In certain embodiments, the invention includes assessing the level of unshielded RN7SL1 RNA in a sample from a subject.