The present disclosure provides methods for sensitizing a cell for modulation by oligomeric compounds. Certain such oligomeric compounds are useful for hybridizing to a complementary nucleic acid, including but not limited, to nucleic acids in a cell. In certain embodiments, hybridization results in modulation of the amount activity or expression of the target nucleic acid in a cell.

The oligonucleotide compositions of the present invention make use of combinations of oligonucleotides. In one aspect, the invention features an oligonucleotide composition including at least 2 different oligonucleotides targeted to a target gene. This invention also provides methods of inhibiting protein synthesis in a cell and methods of identifying oligonucleotide compositions that inhibit synthesis of a protein in a cell.

A method for enhancing, by at least 10 fold, the antibacterial activity of an antisense oligonucleotide composed of morpholino subunits linked by phosphorus-containing intersubunit linkages. The method includes one or both of: conjugating an arginine-rich carrier to a 3′ or 5′ end of the oligonucleotide and modifying the oligonucleotide to contain 20%-50% intersubunit linkages that are positively charged at physiological pH. Also disclosed is an antisense oligonucleotide having enhanced antibacterial activity by virtue of one or both modifications.

Improved DNA vaccine plasmids are disclosed that contain novel immunostimulatory RNA compositions. The improved plasmids eliminate all extraneous sequences, incorporate a novel antibiotic free short RNA based selectable marker, increase eukaryotic expression using a novel chimeric promoter, improve yield and stability during bacterial production, and improve immunostimulation. These vectors are utilized in immunization to elicit improved immune responses or therapy to induce type 1 interferon production.

A method of permeabilizing a cell is disclosed. Kits for permeabilizing cells and analysing RNA contents are also disclosed.

Provided are an engineered CRISPR/Cas12f1 system of which editing efficiency is improved compared to a canonical CRISPR/Cas12f1 system, and a use thereof. A U-rich tail sequence in crRNA is provided that can be introduced into an original guide RNA to improve the editing efficiency of the CRISPR/Cas12f1 system. The U-rich tail sequence has abundant uridine residues at the 3′-ternimus of crRNA, and may further include additional nucleic acids in addition to uridine depending on the environment in which the guide RNA is actually used and the environment in which the guide RNA is expressed. The inventors of the present application described the structure of the U-rich tail sequence, the position of introduction, and the effect thereof with respect to genome editing efficiency.

The promoter of the present invention causes a desired gene to be highly expressed, especially in thermotolerant yeast. The promoter is located upstream of the PIR1 gene or the CTR1 gene on the Kluyveromyces marxianus chromosome and comprises a region controlling expression of the PIR1 gene or the CTR1 gene.

The present disclosure features useful compositions and methods to treat 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 MLH1 activity.

The present invention relates to nucleic acids. In particular, it relates to aptamers capable of binding to a flavivirus structural protein or a flavivirus non-structural protein, useful as therapeutics for preventing, treating and/or diagnosing a flavivirus infection in a patient.

Provided herein are signal activatable molecular constructs for delivery of molecules and related components, compositions, methods, and systems, having a 17 to 30 bp targeting domain duplex RNA, at least one protection strand having a protection segment and linker segment and a sensor strand having a displacement segment and a toehold segment, in which in an inactive conformation the protection segment and the displacement segment form a sensor domain duplex polynucleotide covalently attached to the targeting domain and presenting the toehold segment for binding to a signal molecule. In an active conformation the sensor strand is bound to the signal molecule and is detached from the at least one protection strand and from the targeting domain; and the targeting domain attaches the at least one protection strand in a configuration allowing processing by Dicer and/or an Argonaute enzyme.