Patents by Inventor Mariano A. Garcia-Blanco

Mariano A. Garcia-Blanco 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).

  • Publication number: 20060234247
    Abstract: 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: Application
    Filed: January 21, 2005
    Publication date: October 19, 2006
    Inventors: Madaiah Puttaraju, Edward Otto, Mariano Garcia-Blanco, Gerard McGarrity, Gary Temple, Lloyd Mitchell, Colette Cote, S. Mansfield
  • Publication number: 20060194317
    Abstract: 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: Application
    Filed: May 31, 2005
    Publication date: August 31, 2006
    Inventors: Madaiah Puttaraju, Edward Otto, Mariano Garcia-Blanco, Gerard McGarrity, Gary Temple
  • Publication number: 20060177933
    Abstract: 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: Application
    Filed: January 21, 2005
    Publication date: August 10, 2006
    Inventors: Madaiah Puttaraju, Edward Otto, Mariano Garcia-Blanco, Gerard McGarrity, Gary Temple
  • Publication number: 20060172381
    Abstract: 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 of a protein or polypeptide of interest. 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, and mediate a trans-splicing reaction resulting in the generation of novel chimeric RNA molecule (chimeric RNA) capable of encoding a protein or polypeptide of interest. The invention provides for the in vivo production of chimeric RNA molecules that encode and result in the production of a protein or polypeptide of interest.
    Type: Application
    Filed: October 7, 2005
    Publication date: August 3, 2006
    Inventors: Gerard McGarrity, Mariano Garcia-Blanco
  • Publication number: 20060160182
    Abstract: 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: Application
    Filed: October 7, 2005
    Publication date: July 20, 2006
    Inventors: Gerard McGarrity, Mariano Garcia-Blanco, Madaiah Puttaraju
  • Publication number: 20060154257
    Abstract: 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: Application
    Filed: July 26, 2004
    Publication date: July 13, 2006
    Inventors: Lloyd Mitchell, Madaiah Puttaraju, Mariano Garcia-Blanco, Edward Otto, Yanping Yang
  • Publication number: 20060134658
    Abstract: Methods and compositions for generating novel nucleic acid molecules through trans-splicing that function to reduce the level of expression of a target RNA. 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 primary microRNAs (pri-miRNAs), which are processed in the cell to molecules, referred to as mature miRNA duplex or short interfering RNAs (siRNAs), capable of producing gene silencing by RNA interference (RNAi).
    Type: Application
    Filed: August 9, 2005
    Publication date: June 22, 2006
    Inventor: Mariano Garcia-Blanco
  • Publication number: 20060094110
    Abstract: Methods and compositions for generating novel nucleic acid molecules through targeted spliceosomal mediated trans-splicing that result in expression of an immunogenic polypeptide. The invention includes 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 immunogenic polypeptide, recombinant vector systems capable of expressing the PTMs of the invention, and cells expressing said PTMs. The target pre-mRNA are those encoding proteins that function in antigen uptake, antigen presentation and chaperoning. The methods of the invention encompass contacting the PTMs of the invention with a target pre-mRNA, under conditions in which a portion of the PTM is trans-spliced to a portion of the target pre-mRNA to form a chimeric mRNA molecule capable of encoding an immunogenic polypeptide.
    Type: Application
    Filed: July 29, 2005
    Publication date: May 4, 2006
    Inventors: Gerard McGarrity, Mariano Garcia-Blanco
  • Publication number: 20060088938
    Abstract: 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: Application
    Filed: January 8, 2001
    Publication date: April 27, 2006
    Inventors: Lloyd Mitchell, Mariano Garcia-Blanco
  • Publication number: 20040214263
    Abstract: 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: Application
    Filed: March 20, 2002
    Publication date: October 28, 2004
    Inventors: Lloyd G. Mitchell, S. Gary Mansfield, Madaiah Puttaraju, Rebecca Clark, Mariano A. Garcia-Blanco
  • Publication number: 20040014107
    Abstract: The present invention relates to a method of identifying an RNA, or specific region thereof, to which a protein of interest binds.
    Type: Application
    Filed: May 22, 2003
    Publication date: January 22, 2004
    Inventors: Mariano A. Garcia-Blanco, Somashekarappa Niranjanakumari, Erika L. Lasda, Robert M. Brazas
  • Publication number: 20030153054
    Abstract: 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: Application
    Filed: February 12, 2002
    Publication date: August 14, 2003
    Inventors: Lloyd G. Mitchell, Mariano A. Garcia-Blanco, Madaiah Puttaraju
  • Publication number: 20030148937
    Abstract: 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: Application
    Filed: April 20, 2001
    Publication date: August 7, 2003
    Inventors: S. Gary Mansfield, Lloyd G. Mitchell, Mariano A. Garcia-Blanco, Christopher E. Walsh, Hengjun Chao
  • Publication number: 20030077754
    Abstract: 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: Application
    Filed: January 8, 2001
    Publication date: April 24, 2003
    Inventors: Lloyd G. Mitchell, Mariano A. Garcia-Blanco, Madaiah Puttaraju, S. Gary Mansfield
  • Publication number: 20030027250
    Abstract: 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: Application
    Filed: August 29, 2001
    Publication date: February 6, 2003
    Inventors: Lloyd G. Mitchell, Mariano A. Garcia-Blanco, Carl C. Baker, Madaiah Puttaraju
  • Publication number: 20020193580
    Abstract: 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: Application
    Filed: February 12, 2002
    Publication date: December 19, 2002
    Inventors: Lloyd G. Mitchell, Mariano A. Garcia-Blanco, Madaiah Puttaraju
  • Publication number: 20020115207
    Abstract: 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: Application
    Filed: January 8, 2001
    Publication date: August 22, 2002
    Inventors: Lloyd G. Mitchell, Mariano A. Garcia-Blanco, Madaiah Puttaraju, S. Gary Mansfield
  • Publication number: 20020009755
    Abstract: The present invention relates, in general, to prostatic cancer and, in particular, to a method of monitoring progression of prostate cancer and to a method of treating the disease.
    Type: Application
    Filed: December 17, 1999
    Publication date: January 24, 2002
    Inventors: Mariano A. Garcia-Blanco, Russ P Carstens
  • Patent number: 6280978
    Abstract: 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: Grant
    Filed: September 23, 1998
    Date of Patent: August 28, 2001
    Assignee: Intronn Holdings, LLC
    Inventors: Lloyd G. Mitchell, Mariano A. Garcia-Blanco
  • Patent number: 6083702
    Abstract: 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: Grant
    Filed: August 13, 1998
    Date of Patent: July 4, 2000
    Assignee: Intronn Holdings LLC
    Inventors: Lloyd G. Mitchell, Mariano A. Garcia-Blanco