Biotechnological innovations have vastly improved the capacity to perform large-scale protein studies. The production and interrogation of custom protein libraries has proven important for a plethora of biological applications including multiplexed disease diagnostics, therapeutic antibody discovery, and directed evolution. The present invention relates to methods and compositions for use in making Cas-related fusion protein libraries barcoded with sgRNA sequences for applications in protein studies and for protein self-assembly on surfaces.

The invention relates to iRNA, e.g., double stranded ribonucleic acid (dsRNA), compositions targeting the complement component C5 gene, and methods of using such iRNA, e.g., dsRNA, compositions to inhibit expression of C5 and to treat subjects having a complement component C5-associated disease, e.g., paroxysmal nocturnal hemoglobinuria.

Described herein are compositions and methods for enhancing erythropoiesis in an individual in need thereof. Specifically agents that decrease the expression of Exosc10, such as inhibitory nucleic acid molecules, produce an increase in red blood cell production in the individual.

The invention relates in aspects to hybrid RNAs lacking a poly-A tail and nucleic acid vectors for expressing the RNA. The hybrid RNAs in some instances have a stabilizing triple helical structure. Related methods for expressing RNA in vivo and in vitro are also disclosed.

The present invention relates to the fields of medicine and immunology. In particular, it relates to novel antisense oligonucleotides that may be used in the treatment, prevention and/or delay of Leber congenital amaurosis.

A method of reducing the level of a transcription product in a cell comprising contacting with the cell a composition comprising a double-stranded nucleic acid complex comprising a first nucleic acid strand annealed to a second nucleic acid strand, wherein: (i) the first nucleic acid strand hybridizes to the transcription product and comprises (a) a region consisting of at least 4 consecutive nucleotides that are recognized by RNase H when the strand is hybridized to the transcription product, (b) one or more nucleotide analogs located on 5 terminal side of the region, (c) one or more nucleotide analogs located on 3 terminal side of the region and (d) a total number of nucleotides and nucleotide analogs ranging from 8 to 35 nucleotides and (ii) the second nucleic acid strand comprises (a) nucleotides and optionally nucleotide analogs and (b) at least 4 consecutive RNA nucleotides.

The present invention relates to the fields of medicine and immunology. In particular, it relates to novel antisense oligonucleotides that may be used in the treatment, prevention and/or delay of Leber congenital amaurosis.

Described herein are compositions and methods for enhancing erythropoiesis in an individual in need thereof. Specifically agents that decrease the expression of Exosc8, Exosc9, Dis3, Dis3L or Exosc10, such as inhibitory nucleic acid molecules, produce an increase in red blood cell production in the individual.

Disclosed herein is a triple-stranded nucleic acid comprising a double-stranded nucleic acid and a triplex forming oligonucleotide (TFO), in which the double-stranded nucleic acid comprises a first strand and a second strand complementary to the first strand, and the TFO binds to the first strand. According to some embodiments of the present disclosure, the second strand comprises a plurality of modified nucleotides independently selected from the group consisting of 5-fluoro-uridine, 5-chloro-uridine, 5-bromo-uridine and 5-formyl-uridine nucleotides. Also disclosed herein are kits and methods of detecting a target sequence in a double-stranded nucleic acid.

Described herein are methods of triplex-induced apoptosis, in which multiple triplexes are formed in cells in which gene amplification has occurred (cells comprising/characterized by at least one amplified gene), referred to as target cells, and apoptosis is induced in the target cells.