Abstract:
The present application relates to the use of hybridization chain reaction (HCR) to form double stranded RNA polymers in the presence of a target, such as a nucleic acid associated with a disease or disorder. The RNA polymers are preferably able to activate the RNA-dependent kinase PKR. Activation of PKR via RNA-HCR can be used to treat a wide variety of diseases and disorders by specifically targeting diseased cells.
Abstract:
Described herein are systems and processes for designing the sequence of one or more interacting nucleic acid strands intended to adopt a target secondary structure at equilibrium. The target secondary structure is decomposed into a binary tree and candidate mutations are evaluated on leaf nodes of the tree. During a process of leaf optimization, defect-weighted mutation sampling is used to select each candidate, mutation position with a probability proportional to its contribution to an ensemble defect of the leaf. Subsequences of the tree are then merged, moving up the tree until a final nucleotide sequence of interest is determined that has the target secondary structure at equilibrium.
Abstract:
The present application relates to methods and compositions for triggering RNAi. Triggered RNAi is highly versatile because the silencing targets are independent of the detection targets. In some embodiments, a method of silencing a target gene is provided. The method comprises providing an initiator to a cell comprising a detection target and a silencing target gene, wherein the detection target is different from the silencing target gene; providing a first substrate monomer to the cell, wherein the first substrate monomer comprises a silencing target complement region that is substantially complementary to a portion of the silencing target gene, and an initiator complement region that is substantially complementary to a portion of the initiator; and providing a second substrate monomer to the cell, wherein the second substrate monomer comprises a silencing target region that is substantially complementary to the silencing target complement region; wherein binding of the detection target to the initiator initiates formation of an inactivator double-stranded RNA (inactivator dsRNA) which silences the silencing target gene.
Abstract:
The present invention relates to the use of nucleic acid probes to identify analytes in a sample. In the preferred embodiments, metastable nucleic acid monomers are provided that associate in the presence of an initiator nucleic acid. Upon exposure to the initiator, the monomers self-assemble in a hybridization chain reaction. The initiator nucleic acid may be, for example, a portion of an analyte to be detected or may be part of an initiation trigger such that it is made available in the presence of a target analyte.
Abstract:
The present invention relates to an apparatus and method for quantitative protein design and optimization. In particular, the invention describes the use of Hybrid Exact Rotamer Optimization algorithms in protein design.
Abstract:
The present invention relates to the use of nucleic acid probes to identify analytes in a sample. In the preferred embodiments, metastable nucleic acid monomers are provided that associate in the presence of an initiator nucleic acid. Upon exposure to the initiator, the monomers self-assemble in a hybridization chain reaction. The initiator nucleic acid may be, for example, a portion of an analyte to be detected or may be part of an initiation trigger such that it is made available in the presence of a target analyte.
Abstract:
The present disclosure relates to methods and compositions involving HCR reactions that involve initiators that are split into two or more parts. Effective HCR is dependent upon two or more of these split initiators being brought into proximity (e.g., via binding events mediated by a target) such that a full initiator is formed that is capable of triggering HCR signal amplification.