The present technology relates to the field of drug delivery and provides molecules comprising or consisting of at least one protein-based carrier building block, wherein the protein-based carrier building block comprises at least one, preferably at least two, attachment point(s) or conjugation site(s).

In particular, the technology provides a molecule comprising at least one protein-based building block, wherein the at least one protein-based building block: a) comprises at least one conjugation site or attachment point; b) has a molecular mass of 2.5 to 70 kDa; c) has a globular three-dimensional (3D) structure; d) has a solubility of 10 mg/ml or more, measured in an aqueous solution at room temperature; and
does not specifically bind to any human protein or binds one or more human proteins with a K.sub.D value greater than 510.sup.4 mol/litre.

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.

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 genetic construct is described having a nucleotide sequence A (Cre+ERT2) with a nucleotide sequence SEQ ID NO. 1 coding for an enzyme recombinase Cre and a sequence SEQ ID NO. 2 coding for a mutated receptor for estrogen ERT2; or a nucleotide sequence A with a nucleotide sequence SEQ ID NO. 3 coding for the fragment A of the diphtheria toxin (DTA); and a nucleotide sequence B with a nucleotide sequence SEQ ID NO. 4 coding for the inhibitor of a mutant cyclin dependent kinase (CDK) p27K.

A method of determining sensitivity to cancer treatment includes the step of determining the presence of overexpression of MYC in a biological sample from a patient suffering from cancer, wherein the presence of overexpression of MYC indicates a sensitivity to a treatment by a CDK9 inhibitor and wherein the cancer is selected from the group consisting of carcinoma, leukemia, and lymphoma.

Antisense sequences, including duplex RNAi compositions, which possess improved properties over those taught in the prior art are disclosed. The invention provides optimized antisense oligomer compositions and method for making and using the both in in vitro systems and therapeutically. The invention also provides methods of making and using the improved antisense oligomer compositions.

Antisense sequences, including duplex RNAi compositions, which possess improved properties over those taught in the prior art are disclosed. The invention provides optimized antisense oligomer compositions and method for making and using the both in in vitro systems and therapeutically. The invention also provides methods of making and using the improved antisense oligomer compositions.

The disclosure provides polypeptides comprising an engineered p27, or a fragment thereof such polypeptides may be used to form trimeric protein complexes with a cyclin-dependent kinase 4 (Cdk4) (or a variant thereof) or Cdk6 (or a variant thereof), and a cyclin D (CycD) or a variant thereof.

The present disclosure relates generally to biological entity-protein (e.g. protein-protein) interactions for potential therapeutic applications, and more specifically to high-throughput methods for identifying bridging molecules that induce the formation of recruited biological entity-bridging molecule-target protein complexes to effect said biological entity-protein interactions. The present disclosure also provides methods for using said bridging molecules for treatment of disorders mediated by the target protein of the recruited biological entity-molecule-target protein complex.

A method for analyzing an ability of target nucleic acid sequences to impact gene expression is described. In an embodiment, the method includes cloning the target nucleic acid sequences and associated barcode nucleic acid sequences into a plurality of plasmids, sequencing the plasmids to provide long-read sequencing information based on a target nucleic acid sequence of the target nucleic acid sequences and an associated barcode nucleic acid sequence, associating the target nucleic acid sequence with the associated barcode nucleic acid sequence based on the long-read sequencing information, transducing the plurality of plasmids into a plurality of cells, extracting DNA, total mRNA, and polysome-bound mRNA from the cells, sequencing the barcode nucleic acid sequences in the extracted DNA, total mRNA, and polysome-bound mRNA to provide short-read sequencing information, and analyzing the target nucleic acid sequences by comparing the long-read sequencing information and the short-read sequencing information.