Patents by Inventor Sherman M. Weissman

Sherman M. Weissman 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).

  • Patent number: 10480021
    Abstract: Methods of identifying DNase I Hyper-Resistant Sites (DHRS), or in board sense, highly compact chromatin and characterizing the DNA methylation status of DMRs such as CpG islands and CpG island shores are provided. The methods are particularly useful for analysis of genomic DNA from low quantities of cells, for example, less than 1,000 cells, less than 100 cells, less than 10 cells, or even one cell, and can be used to generate chromatin and methylation profiles. The downstream analyses include in parallel massive sequencing, microarray, PCR and Sanger sequencing, hybridization and other platforms. These methods can be used to generate chromatin and DNA methylation profiles in drug development, diagnostics, and therapeutic applications are also provided.
    Type: Grant
    Filed: June 23, 2015
    Date of Patent: November 19, 2019
    Assignee: YALE UNIVERSITY
    Inventors: Xinghua Pan, Sherman M. Weissman
  • Patent number: 10155038
    Abstract: Compositions and methods of making cells using RNA, and cells made using the disclosed compositions and methods are also provided. In exemplary embodiments, RNA is transfected into cells to effect a molecular, biological, physiological, or histological change in the cells. In preferred embodiments, the RNA is prepared in vitro, more preferably using a DNA template according to the provided compositions and methods. Methods for treating or inhibiting a disorder or disease such cancer are also provided. The methods can include, for example, locally or systemically administering to the host an effective amount of one or more RNAs; or an effective amount of population of cells isolated from the subject or a syngeneic or histocompatible subject, contacted ex vivo with one or RNAs, and optionally expanded. The cells can be, for example, immune cells or stem cells.
    Type: Grant
    Filed: January 27, 2016
    Date of Patent: December 18, 2018
    Assignee: Yale University
    Inventors: Peter M. Rabinovich, Sherman M. Weissman, Marina E. Komarovskaya, Erkut Bahceci, Samuel Katz, Efim Golub
  • Patent number: 10017782
    Abstract: RNA prepared by in vitro transcription using a polymerase chain reaction (PCR)-generated template can be introduced into a cell to modulate cell activity. This method is useful in de-differentiating somatic cells to pluripotent, multipotent, or unipotent cells; re-differentiating stem cells into differentiated cells; or reprogramming of somatic cells to modulate cell activities such as metabolism. Cells can also be transfected with inhibitory RNAs, such as small interfering RNA (siRNA) or micro RNA (miRNA), or combinations thereof to induce reprogramming of somatic cells. For example, target cells are isolated from a donor, contacted with one or more RNA's causing the cells to be de-differentiated, re-differentiated, or reprogrammed in vitro, and administered to a patient in need thereof. The resulting cells are useful for treating one or more symptoms of a variety of diseases and disorders, for organ regeneration, and for restoration of the immune system.
    Type: Grant
    Filed: February 1, 2016
    Date of Patent: July 10, 2018
    Assignee: Yale University
    Inventors: Peter M. Rabinovich, Sherman M. Weissman, Erkut Bahceci, Marina E. Komarovskaya
  • Patent number: 10017761
    Abstract: Methods for preparing cDNA libraries from single and low quantities of cells are disclosed. The methods are based on the principles of multi-strand displacement amplification or semi-random primed polymerase chain reaction. The methods typically include a step of reverse transcription and subsequent amplification of cDNA. The methods can be adapted for preparation of cDNA libraries that are representative of mRNA or whole RNA expressed by the cell or cells. The cDNA is suitable for sequencing or microarray analysis.
    Type: Grant
    Filed: December 23, 2013
    Date of Patent: July 10, 2018
    Assignee: Yale University
    Inventors: Sherman M. Weissman, Xinghua Pan
  • Patent number: 9951349
    Abstract: Compositions for transient but prolonged exogenous mRNA expression through the use of the transcription system of negative strand RNA viruses, and methods of use thereof are disclosed. In some embodiments, the system contains only RNAs and does not include any DNA molecules. The compositions typically include an RNA template unit (rTeUn) that includes a virus regulatory sequences operably linked to a coding sequence of interest. The rTeUn is typically transfected to a host cell's cytoplasm in the presence of virus expression system proteins that mediate replication of the rTeUn and transcription of the transgene. The rTeUn RNA bonded to viral proteins exhibits high resistance to degradation, prolonged duration of expression, and is free of viral genes. The compositions can be used to reprogram cell. For example, the compositions and methods can be used to redirected lymphocytes to target cancer cells, or to dedifferentiate somatic cells into induce pluripotent stem cells.
    Type: Grant
    Filed: September 27, 2012
    Date of Patent: April 24, 2018
    Assignee: Yale University
    Inventors: Peter M. Rabinovich, Sherman M. Weissman
  • Publication number: 20160230188
    Abstract: RNA prepared by in vitro transcription using a polymerase chain reaction (PCR)-generated template can be introduced into a cell to modulate cell activity. This method is useful in de-differentiating somatic cells to pluripotent, multipotent, or unipotent cells; re-differentiating stem cells into differentiated cells; or reprogramming of somatic cells to modulate cell activities such as metabolism. Cells can also be transfected with inhibitory RNAs, such as small interfering RNA (siRNA) or micro RNA (miRNA), or combinations thereof to induce reprogramming of somatic cells. For example, target cells are isolated from a donor, contacted with one or more RNA's causing the cells to be de-differentiated, re-differentiated, or reprogrammed in vitro, and administered to a patient in need thereof. The resulting cells are useful for treating one or more symptoms of a variety of diseases and disorders, for organ regeneration, and for restoration of the immune system.
    Type: Application
    Filed: February 1, 2016
    Publication date: August 11, 2016
    Inventors: Peter M. Rabinovich, Sherman M. Weissman
  • Publication number: 20160151491
    Abstract: Compositions and methods of making cells using RNA, and cells made using the disclosed compositions and methods are also provided. In exemplary embodiments, RNA is transfected into cells to effect a molecular, biological, physiological, or histological change in the cells. In preferred embodiments, the RNA is prepared in vitro, more preferably using a DNA template according to the provided compositions and methods. Methods for treating or inhibiting a disorder or disease such cancer are also provided. The methods can include, for example, locally or systemically administering to the host an effective amount of one or more RNAs; or an effective amount of population of cells isolated from the subject or a syngeneic or histocompatible subject, contacted ex vivo with one or RNAs, and optionally expanded. The cells can be, for example, immune cells or stem cells.
    Type: Application
    Filed: January 27, 2016
    Publication date: June 2, 2016
    Inventors: Peter M. Rabinovich, Sherman M. Weissman, Marina E. Komarovskaya, Erkut Bahceci, Samuel Katz, Efim Golub
  • Patent number: 9249423
    Abstract: RNA prepared by in vitro transcription using a polymerase chain reaction (PCR)-generated template can be introduced into a cell to modulate cell activity. This method is useful in de-differentiating somatic cells to pluripotent, multipotent, or unipotent cells; re-differentiating stem cells into differentiated cells; or reprogramming of somatic cells to modulate cell activities such as metabolism. Cells can also be transfected with inhibitory RNAs, such as small interfering RNA (siRNA) or micro RNA (miRNA), or combinations thereof to induce reprogramming of somatic cells. For example, target cells are isolated from a donor, contacted with one or more RNA's causing the cells to be de-differentiated, re-differentiated, or reprogrammed in vitro, and administered to a patient in need thereof. The resulting cells are useful for treating one or more symptoms of a variety of diseases and disorders, for organ regeneration, and for restoration of the immune system.
    Type: Grant
    Filed: February 2, 2011
    Date of Patent: February 2, 2016
    Assignee: Yale University
    Inventors: Peter M. Rabinovich, Sherman M. Weissman
  • Publication number: 20150368694
    Abstract: Methods of identifying DNase I Hyper-Resistant Sites (DHRS), or in board sense, highly compact chromatin and characterizing the DNA methylation status of DMRs such as CpG islands and CpG island shores are provided. The methods are particularly useful for analysis of genomic DNA from low quantities of cells, for example, less than 1,000 cells, less than 100 cells, less than 10 cells, or even one cell, and can be used to generate chromatin and methylation profiles. The downstream analyses include in parallel massive sequencing, microarray, PCR and Sanger sequencing, hybridization and other platforms. These methods can be used to generate chromatin and DNA methylation profiles in drug development, diagnostics, and therapeutic applications are also provided.
    Type: Application
    Filed: June 23, 2015
    Publication date: December 24, 2015
    Inventors: Xinghua Pan, Sherman M. Weissman
  • Patent number: 8859229
    Abstract: A method of mRNA production for use in transfection is provided, that involves in vitro transcription of PCR generated templates. This RNA can efficiently transfect different kinds of cells. This approach results in increased efficiency (fidelity and productivity) of mRNA synthesis and is less time consuming because it does not require cloning, and also consequently eliminates the unwanted errors and effects related to RNA made on DNA templates obtained with cloning techniques. The results of transfection of RNAs demonstrate that RNA transfection can be very effective in cells that are exceedingly difficult to transfect efficiently with DNA constructs. The method can be used to deliver genes into cells not- or only poorly transfectable for DNA, in vitro and in vivo.
    Type: Grant
    Filed: February 4, 2008
    Date of Patent: October 14, 2014
    Assignee: Yale University
    Inventors: Peter M. Rabinovich, Sherman M. Weissman, Marina E. Komarovskaya, Erkut Bahceci
  • Publication number: 20140249212
    Abstract: Compositions for transient but prolonged exogenous mRNA expression through the use of the transcription system of negative strand RNA viruses, and methods of use thereof are disclosed. In some embodiments, the system contains only RNAs and does not include any DNA molecules. The compositions typically include an RNA template unit (rTeUn) that includes a virus regulatory sequences operably linked to a coding sequence of interest. The rTeUn is typically transfected to a host cell's cytoplasm in the presence of virus expression system proteins that mediate replication of the rTeUn and transcription of the transgene. The rTeUn RNA bonded to viral proteins exhibits high resistance to degradation, prolonged duration of expression, and is free of viral genes. The compositions can be used to reprogram cell. For example, the compositions and methods can be used to redirected lymphocytes to target cancer cells, or to dedifferentiate somatic cells into induce pluripotent stem cells.
    Type: Application
    Filed: September 27, 2012
    Publication date: September 4, 2014
    Applicant: Yale University
    Inventors: Peter M. Rabinovich, Sherman M. Weissman
  • Publication number: 20140213485
    Abstract: Methods for preparing cDNA libraries from single and low quantities of cells are disclosed. The methods are based on the principles of multi-strand displacement amplification or semi-random primed polymerase chain reaction. The methods typically include a step of reverse transcription and subsequent amplification of cDNA. The methods can be adapted for preparation of cDNA libraries that are representative of mRNA or whole RNA expressed by the cell or cells. The cDNA is suitable for sequencing or microarray analysis.
    Type: Application
    Filed: December 23, 2013
    Publication date: July 31, 2014
    Applicant: YALE UNIVERSITY
    Inventors: SHERMAN M. WEISSMAN, XINGHUA PAN
  • Publication number: 20110165133
    Abstract: RNA prepared by in vitro transcription using a polymerase chain reaction (PCR)-generated template can be introduced into a cell to modulate cell activity. This method is useful in de-differentiating somatic cells to pluripotent, multipotent, or unipotent cells; re-differentiating stem cells into differentiated cells; or reprogramming of somatic cells to modulate cell activities such as metabolism. Cells can also be transfected with inhibitory RNAs, such as small interfering RNA (siRNA) or micro RNA (miRNA), or combinations thereof to induce reprogramming of somatic cells. For example, target cells are isolated from a donor, contacted with one or more RNA's causing the cells to be de-differentiated, re-differentiated, or reprogrammed in vitro, and administered to a patient in need thereof. The resulting cells are useful for treating one or more symptoms of a variety of diseases and disorders, for organ regeneration, and for restoration of the immune system.
    Type: Application
    Filed: February 2, 2011
    Publication date: July 7, 2011
    Inventors: Peter M. Rabinovich, Sherman M. Weissman
  • Publication number: 20080260706
    Abstract: A method of mRNA production for use in transfection is provided, that involves in vitro transcription of PCR generated templates with specially designed primers, followed by polyA addition, to produce a construct containing 3? and 5? untranslated sequence (“UTR”), a 5? cap and/or Internal Ribosome Entry Site (IRES), the gene to be expressed, and a polyA tail, typically 50-2000 bases in length. This RNA can efficiently transfect different kinds of cells. This approach results in increased efficiency (fidelity and productivity) of mRNA synthesis and is less time consuming because it does not require cloning, and also consequently eliminates the unwanted errors and effects related to RNA made on DNA templates obtained with cloning techniques. The results of transfection of RNAs demonstrate that RNA transfection can be very effective in cells that are exceedingly difficult to transfect efficiently with DNA constructs.
    Type: Application
    Filed: February 4, 2008
    Publication date: October 23, 2008
    Inventors: Peter M. Rabinovich, Sherman M. Weissman, Marina E. Komarovskaya, Erkut Bahceci
  • Publication number: 20080145364
    Abstract: High throughput assays used to identify antibodies and proteins that induce cell death are described herein. It is not necessary to identify the antigens the antibodies are reactive with prior to performing the assays. Instead, libraries of antibodies and proteins, including murine, human, humanized, single chain, and synthetic antibodies, are screened using high throughput assays to identify those antibodies and proteins which cause cell death. Standard technology is then used to screen for cell viability. Antibodies and proteins which induce apoptosis preferentially or exclusively of cancer cells are then isolated, characterized, and may be cloned. A method for cloning antibodies and proteins has been developed, which provides means for rapid identification of the antibody or protein and the gene encoding the antibody or protein, based on the presence of a “bar code” or “unique sequence.” A method for high throughput production of antibodies to human proteins has also been developed.
    Type: Application
    Filed: February 15, 2006
    Publication date: June 19, 2008
    Inventors: Sherman M. Weissman, Michael Snyder
  • Publication number: 20030082512
    Abstract: The present invention comprises methods of identifying an agent that modulates sterile inflammatory disease by preparing a gene expression profile of a granulocytic cell population isolated from a subject having a sterile inflammatory disease; treating it with an agent; and comparing that profile to a profile prepared from untreated granulocytic cells isolated from a subject known to have sterile inflammatory disease. The invention also includes methods to identify such agents by treating an isolated polymorphonuclear white blood cell population from a patient with a sterile inflammatory disease with an agent and comparing it to a gene expression profile of an untreated polymorponuclear white blood cell population isolated from a patient with a sterile inflammatory disease. Agents that modulate glomerulonephritis are of particular importance.
    Type: Application
    Filed: December 6, 2001
    Publication date: May 1, 2003
    Applicant: GENE LOGIC, INC.
    Inventors: Subrahmanyam V. Yerramilli, Yatindra Prashar, Peter Newburger, Jon Goguen, Sherman M. Weissman
  • Patent number: 6506562
    Abstract: A general method is described for screening cDNAs, genes or genome segments to directly isolate and characterize sequences associated with particular phenotypes. In the case of the human genome, a simplification of the starting material is needed, and a specific method to generate highly polymorphic genome subsets for this purpose is presented. The general screening method identifies DNA sequences containing allele frequency differences when groups with dissimilar phenotypes are compared. The approach is based on mathematical principles of inequality. A change in the abundance ratio of homoduplexes of perfectly matched sequences to heteroduplexes of perfectly matched sequences, or, conversely, of mismatched homoduplexes to mismatched heteroduplexes, serves as an indicator of allele frequency difference.
    Type: Grant
    Filed: October 26, 1999
    Date of Patent: January 14, 2003
    Assignee: Yale University
    Inventors: Sherman M. Weissman, Jon J. Jonsson
  • Publication number: 20020177701
    Abstract: The present invention is directed to an approach to identify changes in gene expression by selective amplification of 3′ fragments of double stranded cDNAs.
    Type: Application
    Filed: September 27, 2001
    Publication date: November 28, 2002
    Applicant: YALE UNIVERSITY
    Inventors: Sherman M. Weissman, Yatindra Prashar
  • Publication number: 20020168658
    Abstract: Methods and compositions are provided to obtain uniform amplification of nucleic acid templates having varied G+C contents.
    Type: Application
    Filed: February 13, 2002
    Publication date: November 14, 2002
    Applicant: YALE UNIVERSITY
    Inventors: Sherman M. Weissman, Namadev Baskaran
  • Patent number: 6395887
    Abstract: The present invention is directed to an approach to identify changes in gene expression by selective amplification of 3′ fragments of double stranded cDNAs.
    Type: Grant
    Filed: November 12, 1997
    Date of Patent: May 28, 2002
    Assignee: Yale University
    Inventors: Sherman M. Weissman, Yatindra Prashar