Efficient sequence specific gene silencing is possible through the use of siRNA technology. By selecting particular siRNAs by rational design, one can maximize the generation of an effective gene silencing reagent, as well as methods for silencing genes. Methods, compositions, and kits generated through rational design of siRNAs are disclosed including those directed to nucleotide sequences for TTR.

Enhanced, specific nucleic acid targeting complexes comprising endo and exonuclease activity, and related methods that allow both targeted degradation of specific and/or non-specific nucleic acids in vivo and specific temporal regulation of nuclease activity to prevent off-target activity are disclosed herein. Through practice of the disclosure, nucleic acids, and cells harboring them, such as cancer cells or pathogens, are selectively degraded in vivo.

The present application discloses a lentiviral transfer system which includes: (i) a self-inactivating transfer vector comprising: multiple gene units, wherein each gene unit includes a heterologous nucleic acid sequence operably linked to a regulatory nucleic acid sequence; and (ii) a helper construct which lacks a 5′ LTR, wherein the 5′ LTR has been replaced with a heterologous promoter, in which the helper construct further comprises: a lentiviral env nucleic acid sequence containing a deletion, wherein the deleted env nucleic acid sequence does not produce functional env protein; and a packaging signal contains a deletion, wherein the deleted packaging signal is nonfunctional.

The present invention is directed to provide novel RNA molecules, chimeric NA molecules, double-stranded RNA molecules, and double-stranded chimeric NA molecules. Specifically, an embodiment of the present invention is an RNA molecule for RNA interference to target a mutant allele with a point mutation, in which (1) the molecule has a nucleotide sequence complementary to a nucleotide sequence of a coding region of the mutant allele; and (2) when counted from the base at the 5′-end in a nucleotide sequence complementary to a nucleotide sequence of the mutant allele, (2-1) a base at position 5 or 6 is mismatched to a base in the mutant allele; (2-2) a position 10 or 11 corresponds to the position of the point mutation; and (2-3) a group at the 2′-position of a pentose at positions 6-8 or positions 7 and 8 is modified with, e.g., OCH.sub.3. In this RNA molecule, one or more ribonucleotides may be replaced by, e.g., a deoxyribonucleotide. The molecule may form a double-stranded RNA with a complementary strand.

Provided are a genome engineering method and a genome engineering kit which can efficiently engineer two or more alleles and are capable of engineering a relatively large region. The present invention provides a genome engineering method for engineering two or more alleles, comprising the steps of: (a) introducing the following (i) and (ii) to a cell comprising the chromosome: (i) a genome engineering system comprising a sequence-specific nucleic acid cleaving molecule targeting a target region in the chromosomal genome, or a polynucleotide encoding the sequence-specific nucleic acid cleaving molecule, and (ii) two or more donor DNAs for selective markers respectively having different selective marker genes (the number of types of the donor DNAs for selective markers are equal to or more than the number of the alleles that are subject to genome engineering); and (b) selecting the cell on the basis of all the selective marker genes carried by the two or more donor DNAs for selective markers.

Methods are disclosed herein for increasing retinal ganglion cell survival in a subject in need thereof. These methods include selecting a subject in need of increased retinal ganglion cell survival and administering a therapeutically effective amount of isolated nanovesicles derived from an extracellular matrix (MBVs) to the subject.

Disclosed herein are conditional siRNAs activatable by CBFβ-MYH11 oncogenic gene and use thereof for treating conditions such as acute myeloid leukemia (AML). The conditional siRNAs target MCL-1 or HDAC8.

The present disclosure relates to an anti-miRNA delivery system, and more specifically, relates to a technique of using a cancer-targeting anti-miRNA delivery system including porous silicon nanoparticles containing anti-miRNA to which a cancer cell surface protein-binding peptide is conjugated, for use in treating cancer. As a result of intensive studies in order to use and apply anti-miR-21 oligonucleotides to the treatment of ovarian cancer, the present inventors confirmed for the first time that when porous silicon nanoparticles containing an anti-miRNA-21 oligonucleotide to which a specific cancer cell surface protein-binding peptide is conjugated are applied, apoptosis is induced in an ovarian cancer cell line and cell viability is reduced, thus, an anti-miRNA delivery system, which is the aforementioned conjugate, is expected to be usefully used as a platform for treating various cancers, especially for treating ovarian cancer.

CRISPR/CAS-related genome editing systems, compositions and methods for targeting the CBLB locus, as well as cells edited using these systems, compositions and methods are provided.

The invention relates to the use of miRNA-193a for regulating gene expression, particularly it relates to the use of miRNA-193a as a CRT agonist, promoting the cell surface expression of CRT. This allows the advantageous treatment of cancers without or with low surface expression of CRT. The invention further relates to compositions comprising the miRNA for use in such treatment.