Defined multi-conjugate oligonucleotides can have predetermined sizes and compositions. For example, in various embodiment, defined multi-conjugate oligonucleotides can have advantageous properties, for example in the form of defined multi-conjugate siRNA (i.e., including two, three or more siRNA) having enhanced intracellular delivery and/or multi-gene silencing effects. In various embodiment, the defined multi-conjugate oligonucleotides can be synthesized via new synthetic intermediates and methods. The defined multi-conjugate oligonucleotides can be used, for example, in reducing gene expression, biological research, treating or preventing medical conditions, or to produce new or altered phenotypes in cells or organisms.

The current invention provides splice-switching compounds with improved characteristics that enhance clinical applicability preferably for treating, ameliorating, preventing, and/or delaying neuromuscular disorders, more specifically DMD.

The present disclosure provides compositions and methods related to nucleic acid molecules having therapeutic aptamers. In particular, the present disclosure provides nucleic acids molecules comprising one or more aptamers having anticoagulant activity, as well as corresponding nucleic acid antidotes, for the modulation of blood coagulation in the context of disease and surgical intervention.

The present invention relates to concatemeric RNA molecules, compositions, particles, and methods of uses thereof.

Described herein are compositions and methods for treating a disease in a subject by administering delivery vectors that express artificial microRNAs, artificial microRNA clusters, and/or a combination of microRNA clusters and associated non-coding RNAs to the subject. Also described herein are methods for preparing artificial microRNAs and artificial microRNA clusters.

Compositions and methods for modulating Kit biological activities are provided. In some embodiments, the presently disclosed subject matter provides antisense oligomers having 10 to 50 linked nucleotides, wherein the antisense oligomer is targeted to a region of a Kit-encoding pre-mRNA, and further wherein the targeted region includes sequences involved in splicing of the Kit-encoding pre-mRNA. Also provided are expression vectors encoding the antisense oligomers disclosed herein, morpholino oligomer derivatives of the presently disclosed antisense oligomers, pharmaceutical compositions that include the disclosed antisense oligomers, expression vectors, and/or morpholino oligomers, and methods for modulating splicing of a Kit pre-RNA in a cell and/or a tissue, inducing apoptosis in mast cells, and treating diseases, disorders, and/or conditions associated with Kit expression.

The present disclosure provides engineered cross-type-nucleic-acid targeting nucleic acids and compositions thereof. Nucleic acid sequences encoding the engineered cross-type-nucleic-acid targeting nucleic acids, as well as expression cassettes, vectors and cells comprising such nucleic acid sequences, are described. Also, methods are disclosed for making and using the engineered cross-type-nucleic-acid targeting nucleic acids and compositions thereof.

A system for adjusting oversubscription loading includes an interface and a processor. The interface is configured to receive a set of performance data from a set of worker systems. The processor is configured to determine a feedback indication for a worker system of the set of worker systems based at least in part on the set of performance data. The feedback indication is used to adjust an oversubscription controller on the worker system. The processor is configured to provide the feedback indication to the worker system.

Provided are aptamers and aptamer compositions and particularly, although not exclusively, to a bi-specific aptamer capable of binding a tumor cell antigen and an immune cell surface protein.

The present invention relates to a RNA molecule comprising a first ribozyme, a first ligation sequence, an effector molecule, a second ligation sequence, and a second ribozyme. Methods of producing circular RNA molecules and treatment methods are also disclosed.