873 results about "RNA molecule" patented technology

The present invention provides lipid-based formulations for delivering, e.g., introducing, nucleic acid-lipid particles comprising an interference RNA molecule to a cell, and assays for optimizing the delivery efficiency of such lipid-based formulations.

Methods are provided for the genetic control of pathogen infestation in host organisms such as plants, vertebrate animals and fungi. Such methods utilize the host as a delivery system for the delivery of genetic agents, preferably in the form of RNA molecules, to a pathogen, which agents cause directly or indirectly an impairment in the ability of the pathogen to maintain itself, grow or otherwise infest a host plant, vertebrate animal or fungus. Also provided are DNA constructs and novel nematode nucleotide sequences for use in same, that facilitate pathogen resistance when expressed in a genetically-modified host. Such constructs direct the expression of RNA molecules substantially homologous and/or complementary to an RNA molecule encoded by a nucleotide sequence within the genome of a pathogen and/or of the cells of a host to effect down-regulation of the nucleotide sequence. Particular hosts contemplated are plants, such as pineapple plants, and particular pathogens are nematodes.

The present invention is directed to controlling pest infestation by inhibiting one or more biological functions in an invertebrate pest. The invention discloses methods and compositions for use in controlling pest infestation by feeding one or more different recombinant double stranded RNA molecules to the pest in order to achieve a reduction in pest infestation through suppression of gene expression. The invention is also directed to methods for making transgenic plants that express the double stranded RNA molecules, and to particular combinations of transgenic pesticidal agents for use in protecting plants from pest infestation.

Provided are microfluidic designs and methods for rapid generation of monodisperse nanoliter volume droplets of reagent/target (e.g., molecule or cell) mix in emulsion oil. The designs and methods enable high-throughput encapsulation of a single target (e.g., DNA/RNA molecules or cells) in controlled size droplets of reagent mix. According to various embodiments, a microfabricated, 3-valve pump is used to precisely meter the volume of reagent/target mix in each droplet and also to effectively route microparticles such as beads and cells into the device, which are encapsulated within droplets at the intersection of the reagent channel and an oil channel. The pulsatile flow profile of the microfabricated pumps provides active control over droplet generation, thereby enabling droplet formation with oils that are compatible with biological reactions but are otherwise difficult to form emulsions with.

The present invention is related to a ribonucleic acid comprising a double stranded structure whereby the double-stranded structure comprises a first strand and a second strand, whereby the first strand comprises a first stretch of contiguous nucleotides and whereby said first stretch is at least partially complementary to a target nucleic acid, and the second strand comprises a second stretch of contiguous nucleotides whereby said second stretch is at least partially identical to a target nucleic acid, and whereby the double stranded structure is blunt ended.

The present invention provides a method for determination of the identity of at least one nucleotide in a RNA-molecule comprising the steps of: (i) providing the RNA-molecule, an oligonucleotide primer binding to a predetermined position of the RNA molecule, a reverse transcriptase, deoxynucleotides and other necessary reagents, in a reaction vessel; (ii) performing a primer extension reaction, whereby the oligonucleotide primer is extended on the RNA-molecule through incorporation of at least one deoxynucleotide by the action of a reverse transcriptase, resulting in the release of a PPi molecule only upon incorporation of a deoxynucleotide; and (iii) detecting the presence or absence of incorporation, thereby indicating the nucleotide identity of the RNA molecule in the relevant position. In a preferred embodiment, the sequencing of the invention is coupled to the Pyrosequencing™ reaction. A variant of the method employs incorporation of modified nucleotides, with an optionally cleavable linker arm to which is attached a label.

The invention concerns with the molecular biology, molecular genetics and biotechnology and can be used in the gene-therapy in the medicine and the agriculture or in the industrial biotechnology for a gene-specific silencing of the disease-related genes or the genes interfering a buildup of a product, respectively. The approach is suggested for changing of genetic properties of an organism by RNA interference leading to gene-specific silencing of a selected gene by RNA molecules, that are complementary in a parallel orientation (pcRNA) to mRNA of the selected gene; pcRNA are synthesized in vivo or in vitro on the artificial DNA sequence possessing symmetrical nucleotide ordering (mirror inversion) in respect to the nucleotide sequence of the gene. The invention suggests the general approach for changing of genetic properties of an organism and is based on the biological properties of mirror inversions of nucleotide sequences that are realized in RNA interference and gene-specific silencing.

The present invention relates in part to methods for suppressing the innate immune response of a cell to transfection with an exogenous nucleic acid, to methods for increasing expression of a protein encoded by an exogenous nucleic acid by repeated delivery of the exogenous nucleic acid to a cell, and to methods of changing the phenotype of a cell by differentiating, transdifferentiating or dedifferentiating cells by repeatedly delivering one or more nucleic acids that encode defined proteins. A method is provided for extended transient transfection by repeated delivery of an in vitro-transcribed RNA (“ivT-RNA”) to a cell to achieve a high and sustained level of expression of a protein encoded by an ivT-RNA transcripts.

The present invention provides novel, serum-stable lipid particles comprising one or more active agents or therapeutic agents, methods of making the lipid particles, and methods of delivering and/or administering the lipid particles. More particularly, the present invention provides serum-stable nucleic acid-lipid particles (SNALP) comprising a nucleic acid (e.g., one or more interfering RNA molecules), methods of making the SNALP, and methods of delivering and/or administering the SNALP (e.g., for the treatment of cancer). In particular embodiments, the present invention provides tumor-directed lipid particles that preferentially target solid tumors. The tumor-directed formulations of the present invention are capable of preferentially delivering a payload such as a nucleic acid to cells of solid tumors compared to non-cancerous cells.

The present invention relates to utrons, RNA molecules which contain promoter regulatory motif(s) and DNA analogs thereof and DNA molecules that can be transcribed to produce the foregoing. In particular, the invention provides gene promoter suppressing nucleic acids which suppress transcription from a promoter of interest. In a preferred embodiment, the invention provides the TSU gene, nucleotide sequences of the TSU gene and RNA, as well as fragments, homologs and derivatives thereof. Methods of isolating TSU genes are also provided. Therapeutic and diagnostic methods and pharmaceutical compositions are also provided. In particular, the invention relates to methods for cell replacement therapy, gene therapy or organ transplantation wherein TSU nucleic acids suppress MHC class I and II gene expression, thus preventing immuno-rejection of non-autologous cells or organs. The invention also provides methods for treatment of diseases or disorders by suppression of MHC class I, MHC class II, ICAM-1, B7-1, B7-2, and/or Fc gamma R expression by provision of TSU function.

This invention generally relates to a method for developing, generating and selecting human embryonic stem (hES)-like pluripotent cells using transgenic expression of intronic microRNA-like RNA agents. More particularly, the present invention relates to a method and composition for generating a non-naturally occurring intron and its intronic components capable of being processed into mir-302-like RNA molecules in mammalian cells and thus inducing certain specific gene silencing effects on differentiation-related and fate-determinant genes of the cells, resulting in reprogramming the cells into a pluripotent embryonic stem (ES)-cell-like state. The ES-like cells so obtained are strongly express hES cell markers, such as Oct3/4, SSEA-3 and SSEA-4, and can be guided into various tissue cell types by treating certain hormones and/or growth factors under a feeder-free cell culture condition in vitro, which may be used for transplantation and gene therapies. Therefore, the present invention offers a simple, effective and safe gene manipulation approach for not only reprogramming somatic cells into ES-like pluripotent cells but also facilitating the maintenance of pluripotent and renewal properties of ES cells under a feeder-free cell culture condition, preventing the tedious retroviral insertion of four large transcription factor genes into one single cell as used in the previous iPS methods.

The present invention relates to compounds, compositions, and methods for the study, diagnosis, and treatment of traits, diseases and conditions that respond to the modulation of Proprotein Convertase Subtilisin Kexin 9 (PCSK9) gene expression and/or activity. The present invention is also directed to compounds, compositions, and methods relating to traits, diseases and conditions that respond to the modulation of expression and/or activity of genes involved in Proprotein Convertase Subtilisin Kexin 9 (PCSK9) gene expression pathways or other cellular processes that mediate the maintenance or development of such traits, diseases and conditions. Specifically, the invention relates to double stranded nucleic acid molecules including small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA) molecules capable of mediating RNA interference (RNAi) against Proprotein Convertase Subtilisin Kexin 9 (PCSK9) gene expression, including cocktails of such small nucleic acid molecules and lipid nanoparticle (LNP) formulations of such small nucleic acid molecules. The present invention also relates to small nucleic acid molecules, such as siNA, siRNA, and others that can inhibit the function of endogenous RNA molecules, such as endogenous micro-RNA (miRNA) (e.g, miRNA inhibitors) or endogenous short interfering RNA (siRNA), (e.g., siRNA inhibitors) or that can inhibit the function of RISC (e.g., RISC inhibitors), to modulate PCSK9 gene expression by interfering with the regulatory function of such endogenous RNAs or proteins associated with such endogenous RNAs (e.g., RISC), including cocktails of such small nucleic acid molecules and lipid nanoparticle (LNP) formulations of such small nucleic acid molecules. Such small nucleic acid molecules and are useful, for example, in providing compositions to prevent, inhibit, or reduce metabolic diseases traits and conditions, including but not limited to hyperlipidemia, hypercholesterolemia, cardiovascular disease, atherosclerosis, hypertension, diabetis (e.g., type I and/or type II diabetis), insulin resistance, obesity and/or other disease states, conditions, or traits associated with PCSK9 gene expression or activity in a subject or organism.

An apparatus and method for performing nucleic acid (DNA and/or RNA) sequencing on a single molecule. The genetic sequence information is obtained by probing through a DNA or RNA molecule base by base at nanometer scale as though looking through a strip of movie film. This DNA sequencing nanotechnology has the theoretical capability of performing DNA sequencing at a maximal rate of about 1,000,000 bases per second. This enhanced performance is made possible by a series of innovations including: novel applications of a fine-tuned nanometer gap for passage of a single DNA or RNA molecule; thin layer microfluidics for sample loading and delivery; and programmable electric fields for precise control of DNA or RNA movement. Detection methods include nanoelectrode-gated tunneling current measurements, dielectric molecular characterization, and atomic force microscopy/electrostatic force microscopy (AFM/EFM) probing for nanoscale reading of the nucleic acid sequences.

The invention relates to the alteration of cell properties using RNA molecules. In particular, it relates to the alteration of the ability of cells to mobilise, migrate, integrate, proliferate and/or differentiate. For example, it relates to the induction of differentiation of stem cells, including the acquisition of the ability to migrate, integrate, and proliferate. It also relates to the induction of in vivo stem cell mobilisation, migration, integration, proliferation and/or differentiation. Accordingly, it relates to the promotion of stem cell-mediated functional repair. The invention also relates to the reversal of differentiation of differentiated cells. All these effects may be effected by providing isolated RNA comprising a RNA sequence extractable from cells comprising the desired cell type(s) to a population of cells under conditions whereby the alteration of the cell property is achieved.