Patents by Inventor Madaiah Puttaraju
Madaiah Puttaraju has filed for patents to protect the following inventions. This listing includes patent applications that are pending as well as patents that have already been granted by the United States Patent and Trademark Office (USPTO).
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Publication number: 20220031731Abstract: The present disclosure provides compounds comprising oligonucleotides complementary to a portion of the LMNA gene. Such compounds are useful for modulating the expression of LMNA in a cell or animal, and in certain instances reducing the amount of progerin mRNA and/or progerin protein. Progerin mRNA results from aberrant splicing of LMNA and is translated to generate progerin protein. Accumulation of progerin protein causes Hutchinson-Gilford progeria syndrome (HOPS), a premature aging disease. In certain embodiments, hybridization of oligonucleotides complementary to a portion of the LMNA gene results in a decrease in the amount of progerin mRNA and/or progerin protein. In certain embodiments, oligonucleotides are used to treat Hutchinson-Gilford Progeria Syndrome.Type: ApplicationFiled: September 20, 2019Publication date: February 3, 2022Applicants: Ionis Pharmaceuticals, Inc., Ionis Pharmaceuticals, Inc.Inventors: Priyam Singh, Frank Rigo, Tom Misteli, Madaiah Puttaraju
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Patent number: 8883753Abstract: Methods and compositions for generating novel nucleic acid molecules through targeted spliceosome mediated RNA trans-splicing that result in expression of a apoAI protein, an apoAI variant, the preferred embodiment referred to herein as the apoAI Milano variant, a pre-pro-apoAI or an analog of apoAI. The methods and compositions include pre-trans-splicing molecules (PTMs) designed to interact with a target precursor messenger RNA molecule (target pre-mRNA) and mediate a trans-splicing reaction resulting in the generation of a novel chimeric RNA molecule (chimeric RNA) capable of encoding apoAI, the apoAI Milano variant, or an analog of apoAI. The expression of this apoAI protein results in protection against vascular disorders resulting from plaque build up, i.e., atherosclerosis, strokes and heart attacks.Type: GrantFiled: June 22, 2011Date of Patent: November 11, 2014Assignee: Virxsys CorporationInventors: Madaiah Puttaraju, Edward Otto, Mariano A. Garcia-Blanco, Gerard J. McGarrity, Gary F. Temple
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Patent number: 8053232Abstract: The present invention provides methods and compositions for generating novel nucleic acid molecules through targeted spliceosomal mediated RNA trans-splicing. The compositions of the invention include pre-trans-splicing molecules (PTMs) designed to interact with a SERPINA1 target precursor messenger RNA molecule (target pre-mRNA) and mediate a trans-splicing reaction resulting in the generation of a novel chimeric RNA molecule (chimeric RNA). In particular, the PTMs of the present invention include those genetically engineered to interact with SERPINA1 target pre-mRNA so as to result in correction of SERPINA1 genetic defects responsible for AAT deficiency. The PTMs of the invention may also comprise sequences that are processed out of the PTM to yield duplex siRNA molecules directed specifically to mutant SERPIN A1 mRNAs. Such duplexed siRNAs are designed to reduce the accumulation of toxic AAT protein in liver cells.Type: GrantFiled: January 21, 2005Date of Patent: November 8, 2011Assignee: VIRxSYS CorporationInventors: Madaiah Puttaraju, Edward Otto, Mariano A. Garcia-Blanco, Gerard J. McGarrity, Gary F. Temple, Lloyd G. Mitchell, Colette Cote, S. Gary Mansfield
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Publication number: 20110263015Abstract: The present invention describes the use of pre-trans-splicing molecules (PTMs) to reprogram human normal and diseased somatic cells into pluripotent stem cells using spliceosome-mediated RNA trans-splicing. More specifically, the present invention describes the use of the SMaRTâ„¢ technology to repair or reprogram the newly induced diseased pluripotent stem cells.Type: ApplicationFiled: August 20, 2009Publication date: October 27, 2011Applicant: VIRXSYS CORPORATIONInventors: Jenice G. D'Costa, Laurent M. Humeau, Stephen Gary Mansfield, Madaiah Puttaraju, Nikolay Korokhov, Gerard J. McGarrity
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Publication number: 20110244519Abstract: The present invention provides methods and compositions for generating novel nucleic acid molecules through RNA trans-splicing that target a highly expressed pre-mRNA and contain the coding sequence for antibody polypeptide(s). The compositions of the invention include pre-trans-splicing molecules (PTMs) designed to interact with the target precursor messenger RNA molecule (target pre-mRNA) that is abundantly expressed or tumor specific and mediate a trans-splicing reaction resulting in the generation of novel chimeric RNA molecule (chimeric RNA) capable of encoding an antibody polypeptide. The invention provides for the in vivo production of chimeric RNA molecules that encode and result in the production of an antibody polypeptide that is therapeutically effective against, for example, infectious agents, cancer cells, transplantation antigens, rheumatoid arthritis, etc.Type: ApplicationFiled: January 11, 2011Publication date: October 6, 2011Applicant: VIRxSYS CorporationInventors: Gerard J. McGarrity, Mariano A. Garcia-Blanco, Madaiah Puttaraju
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Patent number: 7968334Abstract: Methods and compositions for generating novel nucleic acid molecules through targeted spliceosome mediated RNA trans-splicing that result in expression of a apoAI protein, an apoAI variant, the preferred embodiment referred to herein as the apoAI Milano variant, a pre-pro-apoAI or an analogue of apoAI. The methods and compositions include pre-trans-splicing molecules (PTMs) designed to interact with a target precursor messenger RNA molecule (target pre-mRNA) and mediate a trans-splicing reaction resulting in the generation of a novel chimeric RNA molecule (chimeric RNA) capable of encoding apoAI, the apoAI Milano variant, or an analogue of apoAI. The expression of this apoAI protein results in protection against vascular disorders resulting from plaque build up, i.e., atherosclerosis, strokes and heart attacks.Type: GrantFiled: May 31, 2005Date of Patent: June 28, 2011Assignee: VIRxSYS CorporationInventors: Madaiah Puttaraju, Edward Otto, Mariano A. Garcia-Blanco, Gerard J. McGarrity, Gary F. Temple
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Patent number: 7879321Abstract: The present invention provides methods and compositions for generating novel nucleic acid molecules through RNA trans-splicing that target a highly expressed pre-mRNA and contain the coding sequence for antibody polypeptide(s). The compositions of the invention include pre-trans-splicing molecules (PTMs) designed to interact with the target precursor messenger RNA molecule (target pre-mRNA) that is abundantly expressed or tumor specific and mediate a trans-splicing reaction resulting in the generation of novel chimeric RNA molecule (chimeric RNA) capable of encoding an antibody polypeptide. The invention provides for the in vivo production of chimeric RNA molecules that encode and result in the production of an antibody polypeptide that is therapeutically effective against, for example, infectious agents, cancer cells, transplantation antigens, rheumatoid arthritis, etc.Type: GrantFiled: October 7, 2005Date of Patent: February 1, 2011Assignee: VIRxSYS CorporationInventors: Gerard J. McGarrity, Mariano A. Garcia-Blanco, Madaiah Puttaraju
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Publication number: 20060246422Abstract: The molecules and methods of the present invention provide a means for in vivo production of a trans-spliced molecule in a selected subset of cells. The pre-trans-splicing molecules of the invention are substrates for a trans-splicing reaction between the pre-trans-splicing molecules and a pre-mRNA that is uniquely expressed in the specific target cells. The in vivo trans-splicing reaction provides a novel mRNA that is functional as mRNA or encodes a protein to be expressed in the target cells. The expression product of the mRNA is a protein of therapeutic value to the cell or host organism, a toxin that kills the specific cells or a novel protein not normally present in such cells. The invention further provides PTMs that have been genetically engineered for the identification of exon/intron boundaries of pre-mRNA molecules using an exon tagging method.Type: ApplicationFiled: October 21, 2005Publication date: November 2, 2006Inventors: Lloyd Mitchell, Mariano Garcia-Blanco, Carl Baker, Madaiah Puttaraju
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Publication number: 20060234247Abstract: The present invention provides methods and compositions for generating novel nucleic acid molecules through targeted spliceosomal mediated RNA trans-splicing. The compositions of the invention include pre-trans-splicing molecules (PTMs) designed to interact with a SERPINA1 target precursor messenger RNA molecule (target pre-mRNA) and mediate a trans-splicing reaction resulting in the generation of a novel chimeric RNA molecule (chimeric RNA). In particular, the PTMs of the present invention include those genetically engineered to interact with SERPINA1 target pre-mRNA so as to result in correction of SERPINA1 genetic defects responsible for AAT deficiency. The PTMs of the invention may also comprise sequences that are processed out of the PTM to yield duplex siRNA molecules directed specifically to mutant SERPIN A1 mRNAs. Such duplexed siRNAs are designed to reduce the accumulation of toxic AAT protein in liver cells.Type: ApplicationFiled: January 21, 2005Publication date: October 19, 2006Inventors: Madaiah Puttaraju, Edward Otto, Mariano Garcia-Blanco, Gerard McGarrity, Gary Temple, Lloyd Mitchell, Colette Cote, S. Mansfield
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Publication number: 20060194317Abstract: Methods and compositions for generating novel nucleic acid molecules through targeted spliceosome mediated RNA trans-splicing that result in expression of a apoAI protein, an apoAI variant, the preferred embodiment referred to herein as the apoAI Milano variant, a pre-pro-apoAI or an analogue of apoAI. The methods and compositions include pre-trans-splicing molecules (PTMs) designed to interact with a target precursor messenger RNA molecule (target pre-mRNA) and mediate a trans-splicing reaction resulting in the generation of a novel chimeric RNA molecule (chimeric RNA) capable of encoding apoAI, the apoAI Milano variant, or an analogue of apoAI. The expression of this apoAI protein results in protection against vascular disorders resulting from plaque build up, i.e., atherosclerosis, strokes and heart attacks.Type: ApplicationFiled: May 31, 2005Publication date: August 31, 2006Inventors: Madaiah Puttaraju, Edward Otto, Mariano Garcia-Blanco, Gerard McGarrity, Gary Temple
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Publication number: 20060177933Abstract: The present invention provides methods and compositions for generating novel nucleic acid molecules through targeted spliceosome mediated RNA trans-splicing that result in expression of an apoA-1 variant, the preferred embodiment referred to herein as the apoA-1 Milano variant. The compositions of the invention include pre-trans-splicing molecules (PTMs) designed to interact with a target precursor messenger RNA molecule (target pre-mRNA) and mediate a trans-splicing reaction resulting in the generation of a novel chimeric RNA molecule (chimeric RNA) capable of encoding the apoA-1 Milano variant. The expression of this variant protein results in protection against vascular disorders resulting from plaque build up, i.e., strokes and heart attacks. In particular, the PTMs of the present invention include those genetically engineered to interact with the apoA-1 target pre-mRNA so as to result in expression of the apoA-1 Milano variant.Type: ApplicationFiled: January 21, 2005Publication date: August 10, 2006Inventors: Madaiah Puttaraju, Edward Otto, Mariano Garcia-Blanco, Gerard McGarrity, Gary Temple
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Publication number: 20060160182Abstract: The present invention provides methods and compositions for generating novel nucleic acid molecules through RNA trans-splicing that target a highly expressed pre-mRNA and contain the coding sequence for antibody polypeptide(s). The compositions of the invention include pre-trans-splicing molecules (PTMs) designed to interact with the target precursor messenger RNA molecule (target pre-mRNA) that is abundantly expressed or tumor specific and mediate a trans-splicing reaction resulting in the generation of novel chimeric RNA molecule (chimeric RNA) capable of encoding an antibody polypeptide. The invention provides for the in vivo production of chimeric RNA molecules that encode and result in the production of an antibody polypeptide that is therapeutically effective against, for example, infectious agents, cancer cells, transplantation antigens, rheumatoid arthritis, etc.Type: ApplicationFiled: October 7, 2005Publication date: July 20, 2006Inventors: Gerard McGarrity, Mariano Garcia-Blanco, Madaiah Puttaraju
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Publication number: 20060154257Abstract: The present invention provides methods and compositions for rapid high capacity functional screening to identify optimal pre-trans-splicing molecules (PTMs). The compositions of the invention include PTM expression libraries capable of encoding candidate PTMs designed to interact with a target precursor messenger RNA molecule (target pre-mRNA) and mediate a trans-splicing reaction resulting in the generation of a novel chimeric RNA molecule (chimeric RNA). The candidate PTMs of the invention encode a portion of a first reporter molecule and may encode one or more other reporter molecules, which can be used to select for cells expressing optimal PTMs (efficient and specific). The compositions of the invention also include cells that express a target pre-mRNA encoding the remaining portion of the first reporter molecule.Type: ApplicationFiled: July 26, 2004Publication date: July 13, 2006Inventors: Lloyd Mitchell, Madaiah Puttaraju, Mariano Garcia-Blanco, Edward Otto, Yanping Yang
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Publication number: 20040248141Abstract: The present invention provides methods and compositions for generating novel nucleic acid molecules through targeted spliceosomal mediated RNA trans-splicing. The compositions of the invention include pre-trans-splicing molecules (PTMs) designed to interact with a target precursor messenger RNA molecule (target pre-mRNA) and mediate a trans-splicing reaction resulting in the generation of a novel chimeric RNA molecule (chimeric RNA). In particular, the PTMs of the present invention can be genetically engineered to interact with a specific target pre-mRNA expressed in cells of the skin so as to result in correction of genetic defects responsible for a variety of different skin disorders to encode a reporter molecule or protein that may have therapeutic benefit. The compositions of the invention further include recombinant vectors systems capable of expressing the PTMs of the invention and cells expressing said PTMs.Type: ApplicationFiled: July 17, 2003Publication date: December 9, 2004Inventors: Lloyd G. Mitchell, Madaiah Puttaraju, Guenter Dallinger, Alfred Klausegger, Johann Bauer
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Publication number: 20040214263Abstract: The invention provides molecules and methods for in vivo production of a trans-spliced molecule in selected cells. Pre-trans-splicing molecules of the invention are substrates for a trans-splicing reaction between the pre-trans-splicing molecules and a pre-mRNA which is uniquely expressed in the specific target cells. The in vivo trans-splicing reaction provides a novel mRNA which is functional as mRNA or encodes a protein to be expressed in the target cells. The mRNA expression product is a therapeutic protein, a toxin which causes killing of the specific cells, or a novel protein not normally present in such cells. The invention further provides genetically engineered PTMs for the identification of exon/intron boundaries of pre-mRNA molecules using an exon tagging method. The PTMs of the invention can also be designed to produce chimeric RNA encoding peptide affinity purification tags which can be used to purify and identify proteins expressed in a specific cell type.Type: ApplicationFiled: March 20, 2002Publication date: October 28, 2004Inventors: Lloyd G. Mitchell, S. Gary Mansfield, Madaiah Puttaraju, Rebecca Clark, Mariano A. Garcia-Blanco
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Publication number: 20040018622Abstract: The present invention provides methods and compositions for generating novel nucleic acid molecules through targeted spliceosomal mediated RNA trans-splicing. The compositions of the invention include pre-trans-splicing molecules (PTMs) designed to interact with a target precursor messenger RNA molecule (target pre-mRNA) and mediate a trans-splicing reaction resulting in the generation of a novel chimeric RNA molecule (chimeric RNA). In particular, the PTMs of the present invention are genetically engineered to interact with a specific target pre-mRNA expressed in cells of the skin so as to result in correction of genetic defects responsible for a variety of different skin disorders. The compositions of the invention further include recombinant vectors systems capable of expressing the PTMs of the invention and cells expressing said PTMs.Type: ApplicationFiled: July 17, 2002Publication date: January 29, 2004Inventors: Lloyd G. Mitchell, Madaiah Puttaraju, Guenter Dallinger, Alfred Klausegger, Johann Bauer
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Publication number: 20030204861Abstract: The present invention relates to development of an animal model system for in vivo testing of spliceosome-mediated RNA trans-splicing reactions. The present invention provides transgenic animals, and methods for generating such animals, that have been genetically engineered to expresses a target precursor messenger RNA molecule (target pre-mRNA) that serves as a substrate for a trans-splicing reaction. Specifically, the transgenic animals contain at least one transgene capable of expressing a target pre-mRNA molecule. The invention provides methods, based on utilization of the transgenic animals, for assessing the specificity and efficiency of a pre-trans-splicing molecule (PTM) designed to interact with a target pre-mRNA and mediate a trans-splicing reaction resulting in the generation of a novel chimeric RNA molecule. The present invention further relates to the transgenic expression of PTM molecules in animals to determine gene function, i.e, functional genetics.Type: ApplicationFiled: April 30, 2002Publication date: October 30, 2003Inventors: Madaiah Puttaraju, Lloyd G. Mitchell, John F. Engelhardt, Xiaoming Liu
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Publication number: 20030153054Abstract: The present invention provides methods and compositions for delivery of synthetic pre-trans-splicing molecules (synthetic PTMs) into a target cell. The compositions of the invention include synthetic pre-trans-splicing molecules (PTMs) with enhanced stability against chemical and enzymatic degradation. The synthetic PTMs are designed to interact with a natural target precursor messenger RNA molecule (target pre-mRNA) and mediate a trans-splicing reaction resulting in the generation of a novel chimeric RNA molecule (chimeric RNA).Type: ApplicationFiled: February 12, 2002Publication date: August 14, 2003Inventors: Lloyd G. Mitchell, Mariano A. Garcia-Blanco, Madaiah Puttaraju
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Publication number: 20030077754Abstract: The molecules and methods of the present invention provide a means for in vivo production of a trans-spliced molecule in a selected subset of cells. The pre-trans-splicing molecules of the invention are substrates for a trans-splicing reaction between the pre-trans-splicing molecules and a pre-mRNA which is uniquely expressed in the specific target cells. The in vivo trans-splicing reaction provides a novel mRNA which is functional as mRNA or encodes a protein to be expressed in the target cells. The expression product of the mRNA is a protein of therapeutic value to the cell or host organism a toxin which causes killing of the specific cells or a novel protein not normally present in such cells. The invention further provides PTMs that have been genetically engineered for the identification of exon/intron boundaries of pre-mRNA molecules using an exon tagging method.Type: ApplicationFiled: January 8, 2001Publication date: April 24, 2003Inventors: Lloyd G. Mitchell, Mariano A. Garcia-Blanco, Madaiah Puttaraju, S. Gary Mansfield
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Publication number: 20030027250Abstract: The molecules and methods of the present invention provide a means for in vivo production of a trans-spliced molecule in a selected subset of cells. The pre-trans-splicing molecules of the invention are substrates for a trans-splicing reaction between the pre-trans-splicing molecules and a pre-mRNA which is uniquely expressed in the specific target cells. The in vivo trans-splicing reaction provides a novel mRNA which is functional as mRNA or encodes a protein to be expressed in the target cells. The expression product of the mRNA is a protein of therapeutic value to the cell or host organism a toxin which causes killing of the specific cells or a novel protein not normally present in such cells. The invention further provides PTMs that have been genetically engineered for the identification of exon/intron boundaries of pre-mRNA molecules using an exon tagging method.Type: ApplicationFiled: August 29, 2001Publication date: February 6, 2003Inventors: Lloyd G. Mitchell, Mariano A. Garcia-Blanco, Carl C. Baker, Madaiah Puttaraju