Abstract: Disclosed herein are conditional siRNAs activatable by pro-hypertrophic RNA sequences and use thereof for treating conditions such as cardiac hypertrophy. The conditional siRNAs target calcineurin or HDAC2.

Abstract: The current invention provides a synthetic prokaryotic genome comprising 5 or fewer occurrences of one or more sense codons; and/or a synthetic prokaryotic genome derived from a parent genome, wherein the synthetic prokaryotic genome comprises less than 10%, 5%, 2%, 1%, 0.5%, 0.1% of the occurrences of one or more sense codons, relative to the parent genome; and/or a synthetic prokaryotic genome comprising 100 or more, 200 or more, or 1000 or more genes with no occurrences of one or more sense codons.

Abstract: The present invention relates to methods of administering to a subject multimeric oligonucleotides having monomeric subunits joined by linkers. The multimeric oligonucleotides have a molecular weight of at least about 45 kD and other characteristics, such that their clearance due to glomerular filtration is reduced. The present invention also relates to such multimeric oligonucleotides and methods of synthesizing such multimeric oligonucleotides.

Abstract: The current invention provides a synthetic prokaryotic genome comprising 5 or fewer occurrences of one or more sense codons; and/or a synthetic prokaryotic genome derived from a parent genome, wherein the synthetic prokaryotic genome comprises less than 10%, 5%, 2%, 1%, 0.5%, 0.1% of the occurrences of one or more sense codons, relative to the parent genome; and/or a synthetic prokaryotic genome comprising 100 or more, 200 or more, or 1000 or more genes with no occurrences of one or more sense codons.

Abstract: The present disclosure provides methods of treating subjects having sepsis, SIRS, septic shock, and/or MODS, methods of identifying subjects having an increased risk of developing sepsis, SIRS, septic shock, and/or MODS, and methods of detecting Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) and/or Low Density Lipoprotein Receptor (LDLR) variant nucleic acid molecules and variant polypeptides.

Abstract: The present invention relates to RNAi agents, e.g., double stranded RNA (dsRNA) agents, targeting the complement component C3 gene (C3). The invention also relates to methods of using such RNAi agents to inhibit expression of a C3 gene and to methods of preventing and treating a C3-associated disorder, e.g., cold agglutinin disease (CAD), warm autoimmune hemolytic anemia, and paroxysmal nocturnal hemoglobinuria (PNH), lupis nephritis (LN), bullous pemphigoid, Pemphigus, e.g., Pemphigus vulgaris (PV) and Pemphigus foliaceus (PF), and C3 glomerulopathy.

Abstract: Disclosed herein are compositions and pharmaceutical formulations that comprise a binding moiety conjugated to a modified polynucleic acid molecule and a polymer. Also described herein include methods for treating a cancer which utilize a composition or a pharmaceutical formulation comprising a binding moiety conjugated to a polynucleic acid molecule and a polymer.

Abstract: This invention relates generally to pharmaceutical compositions and preparations of circular polyribonucleotides and uses thereof.

Abstract: Described herein are synthetic inducible promoters including 5?-(UP element)-(?35 element)-(spacer element)-(?10 element)-(discriminator element)-3?. Also included are vectors, ?-Proteobacteria strains and ?-Proteobacteria strains including the synthetic inducible promoters. A Mobile-CRISPRi plasmid and methods of partially or fully knocking-down expression of a gene in ?-Proteobacteria or ?-Proteobacteria are also described. Further included are methods of making an ?-Proteobacteria or ?-Proteobacteria strain.

Abstract: A method of sequencing a polynucleotide strand can include providing the polynucleotide strand with a primer annealed thereto and a polymerase operably bound to the polynucleotide strand; successively exposing the polynucleotide strand to the flow of four different dNTPs according to a first predetermined ordering; and successively exposing the polynucleotide strand to the flow of four different dNTPs according to a second predetermined ordering, wherein the second predetermined ordering is different from the first predetermined ordering.

Abstract: The present disclosure relates, generally, to compositions and methods for producing, purifying, and using circular RNA.

Abstract: The methods and assays described herein relate to detection, diagnosis, and treatment of lung cancer, e.g., by detecting the level of expression of certain miRNAs described herein and/or by therapeutically increasing the level of those miRNAs.

Abstract: An efficient synthesis and assembly method for the large fragment DNA based on the programmable nuclease Argonaute, specifically includes: constructing and treating antibiotic resistance gene reconstructed vectors with linearization, dividing a target DNA into multiple small DNA fragments and then synthesizing the small DNA fragments, followed by loading the synthesized small DNA fragments to the antibiotic resistance gene reconstructed vectors; and the SLIC and resistance gene reconstruction are used to achieve assembly of the target DNA. The method combines the SLIC with a resistance gene reconstruction strategy, allowing for the assembly of 5-6 small fragments in a single resistance gene reconstruction, which is more efficient and time-saving. Moreover, the number of the resistance gene reconstructions can be flexibly chosen according to the length of the DNA fragments. Mutations are not introduced caused by PCR, and the reconstructed large fragment do not need a second sequencing, saving time and costs.

Abstract: Novel cytotoxic fluoropyrimidine polymers for treating cancer (e.g., colorectal cancer (CRC)) in a subject (e.g., a subject having cancer) are nucleic acid molecules including 5-fluoro-2?deoxyuridine monophosphate (FdUMP)[10] having a polyethylene glycol (PEG) spacer appended to the 5? terminus and a cytarabine (AraC) nucleotide appended to 3?termius. These novel cytotoxic fluoropyrimidine polymers may be used in compositions, kits and methods for treating advanced and high-risk cancers, including CRC.

Abstract: The present invention is directed to a storage-stable formulation of long-chain RNA. In particular, the invention concerns a dry powder composition comprising a long-chain RNA molecule. The present invention is furthermore directed to methods for preparing a dry powder composition comprising a long-chain RNA molecule by spray-drying. The invention further concerns the use of such a dry powder composition comprising a long-chain RNA molecule in the preparation of pharmaceutical compositions and vaccines, to a method of treating or preventing a disorder or a disease, to first and second medical uses of such a dry powder composition comprising a long-chain RNA molecule and to kits, particularly to kits of parts, comprising such a dry powder composition comprising a long-chain RNA molecule.

Abstract: The present disclosure relates to methods, formulations and devices for the delivery and therapeutic administration of polynucleotides encoding AADC. The present disclosure relates to methods, formulations and devices for the delivery and therapeutic administration of AAV vectors which include polynucleotides encoding AADC. The present disclosure relates to methods, formulations and devices for the delivery and therapeutic administration of polynucleotides encoding AADC in the treatment of neurological diseases, disorders and conditions, including Parkinson's Disease.

Abstract: The disclosed technology includes methods of treating Danon disease, for example correcting genetic mutations in the LAMP-2 gene and ameliorating at least one Danon disease phenotype, for example defective LAMP-2B-mediated autophagy. In some implementations, the disclosed methods include editing a mutated form of the LAMP-2 gene in a patient in need thereof. In some implementations, editing the mutated form of the LAMP-2 gene may include use of a CRISPR editing technique targeted to the mutated form of the LAMP-2 gene. As a result, mutated LAMP-2 proteins in mammalian subjects may be restored in at least some of the affected cells, for example cardiomyocytes.

Abstract: Disclosed herein are compositions comprising an oligonucleotide that targets MST1. The oligonucleotide may include a small interfering RNA (siRNA) or an antisense oligonucleotide (ASO). Also provided herein are methods of treating conditions associated with MST1 variants that include providing an oligonucleotide that targets MST1 to a subject.

Abstract: The present disclosure features useful compositions and methods to treat nucleotide repeat expansion disorders, e.g., in a subject in need thereof. In some aspects, the compositions and methods described herein are useful in the treatment of disorders associated with MSH3 activity.

Abstract: Provided herein are methods, compounds, and compositions for reducing expression of huntingtin mRNA and protein in an animal. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate Huntington's disease, or a symptom thereof.