Patents by Inventor Joseph M. Jacobson

Joseph M. Jacobson 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: 20220162620
    Abstract: Applications of a Streptococcus Cas9 ortholog from Streptococcus macacae (Smac Cas9), possessing minimal adenine-rich PAM specificity, include an isolated Streptococcus macacae Cas9 protein or transgene expression thereof, a CRISPR-associated DNA endonuclease with PAM interacting domain amino acid sequences that are at least 80% identical to that of the isolated Streptococcus macacae Cas9 protein, and an isolated, engineered Streptococcus pyogenes Cas9 (Spy Cas9) protein with a PID as either the PID amino acid composition of the isolated Streptococcus macacae Cas9 (Smac Cas9) protein or of a CRISPR-associated DNA endonuclease with PID amino acid sequences that are at least 80% identical to that of the isolated Streptococcus macacae Cas9 protein. A method for altering expression of at least one gene product employs Streptococcus macacae Cas9 endonucleases in complex with guide RNA, for specific recognition and activity on a DNA target immediately upstream of either an “NAA” or “NA” or “NAAN” PAM sequence.
    Type: Application
    Filed: May 6, 2019
    Publication date: May 26, 2022
    Applicant: Massachusetts Institute of Technology
    Inventors: Pranam Chatterjee, Noah Michael Jakimo, Joseph M Jacobson
  • Patent number: 11326209
    Abstract: The present invention relates to a cell based genomic Recorded Accumulative Memory (geRAM) system (also referred to herein as Genomically Encoded Memory (GEM)) for recoding data (i.e., changes in nucleic acid sequences in cellular DNA in response to physical and/or chemical signal(s)) from the cellular environment.
    Type: Grant
    Filed: November 7, 2014
    Date of Patent: May 10, 2022
    Assignees: Massachusetts Institute of Technology, Whitehead Institute of Biomedical Research
    Inventors: Joseph M. Jacobson, Noah Jakimo, Naama Kanarek, David Sabatini
  • Patent number: 11268115
    Abstract: In a method for generating an elongated nucleic acid molecule, a nucleic acid addition of a first nucleic acid molecule attached to a first 3? or 5? protecting group to a nucleic acid immobilized on a surface produces an intermediate-length immobilized nucleic acid. The first protecting group is dissociated from the first nucleic acid molecule. A second nucleic acid molecule that is attached to a second associated a 3? or 5? associated protecting group is added to the intermediate-length nucleic acid. The second associated protecting group is dissociated from the second nucleic acid molecule. A sequentially-extended elongated immobilized nucleic acid molecule having a desired sequence and length is produced by sequentially extending the intermediate-length immobilized nucleic acid by adding additional nucleic acid molecules with associated protecting groups to the intermediate-length nucleic acid and dissociating the associated protecting group after each addition.
    Type: Grant
    Filed: November 22, 2016
    Date of Patent: March 8, 2022
    Assignee: Massachusetts Institute of Technology
    Inventors: Peter A. Carr, Brian Y. Chow, Joseph M. Jacobson, David W. Mosley, Christopher Emig
  • Publication number: 20220025341
    Abstract: Methods and compositions relating to an engineered peptide capable of binding to an infectious biological molecule for inhibition by mediated degradation using the ubiquitin proteasome pathway. The engineered peptide includes a targeting domain and an ubiquitin ligase recruiting domain. The engineered peptide includes a targeting domain and an ubiquitin ligase. The targeting domain is computationally-derived from a known receptor for the infectious biological molecule. The engineered peptide is optimized for minimal size and minimum off-target effects.
    Type: Application
    Filed: May 28, 2021
    Publication date: January 27, 2022
    Inventors: Pranam CHATTERJEE, Joseph M. JACOBSON
  • Publication number: 20220002700
    Abstract: Methods and compositions relating to an engineered peptide capable of binding to a biological molecule for viral inhibition. The engineered peptide is computationally-derived from soluble angiotensin-converting enzyme 2 (sACE2), a known receptor for viral spike proteins. The engineered peptide is optimized for minimal size and off-target effects. The engineered sACE2 peptide variants are a suitable targeting domain for fusion proteins of various effects.
    Type: Application
    Filed: April 5, 2021
    Publication date: January 6, 2022
    Inventors: Pranam CHATTERJEE, Raghava Manvitha PONNAPATI, Eyal PERRY, Joseph M. JACOBSON
  • Publication number: 20210350879
    Abstract: A DNA canvas comprising a plurality of uniquely-coded polymer strands immobilized on a substrate can be used to provide a reference map comprising a set of reference association polymers having a dual-barcode generated by nondestructively associating spatially-adjacent polymers on the DNA canvas, encoding digital information on the DNA canvas to provide a patterned DNA canvas by disabling a pattern of selected plurality of polymers strands to provide a set of data association polymers having a single bar code that corresponds to a single bit in the bitmap. The digital information capable of being retrieved by sequencing the set of reference and data association polymers, computationally recovering spatial locations of each of the selected polymer strands that were disabled and recovering the bitmap encoded in the pattern of disabled polymer strands by comparison of the set of reference association polymer sequences to the set of data association polymer sequences.
    Type: Application
    Filed: May 11, 2021
    Publication date: November 11, 2021
    Inventors: Eyal PERRY, Junichi OGAWA, Joseph M. JACOBSON
  • Publication number: 20210324382
    Abstract: A chimeric DNA:RNA guide for very high accuracy Cas9 genome editing employs nucleotide-type substitutions in nucleic acid-guided endonucleases for enhanced specificity. The CRISPR-Cas9 gene editing system is manipulated to generate chimeric DNA:RNA guide strands to minimize the off-target cleavage events of the S. pyogenes Cas9 endonuclease. A DNA:RNA chimeric guide strand is sufficient to guide Cas9 to a specified target sequence for indel formation and minimize off-target cleavage events due to the specificity conferred by DNA-DNA interactions. Use of chimeric mismatch-evading lowered-thermostability guides (“melt-guides”) demonstrate that nucleotide-type substitutions in the spacer can reduce cleavage of sequences mismatched by as few as a single base pair. The chimeric mismatch-evading lowered-thermostability guides replace most gRNA spacer positions with DNA bases to suppress mismatched targets under Cas9's catalytic threshold.
    Type: Application
    Filed: January 22, 2021
    Publication date: October 21, 2021
    Applicant: Massachusetts Institute of Technology
    Inventors: Noah Jakimo, Pranam Chatterjee, Joseph M. Jacobson
  • Patent number: 10975406
    Abstract: The invention provides compositions and methods for repeatable directed endonucleases (RDEs) and methods for repeatedly, and specifically cleaving DNA offset from the RDE's DNA recognition sequence on the target nucleic acid rather than within the DNA recognition sequence. Conservation of the recognition sequence of the target nucleic acid enables for re-localization of an RDE back to the DNA recognition sequence for further cleavage. The RDEs and methods of the invention are useful in applications including, but not limited to, recording data into a genome, timing the order of biochemical pathway events, efficient genome engineering and encoding lagged cellular death.
    Type: Grant
    Filed: July 15, 2015
    Date of Patent: April 13, 2021
    Assignee: Massachusetts Institute of Technology
    Inventors: Joseph M. Jacobson, Noah Michael Jakimo
  • Publication number: 20210046697
    Abstract: A 3D object according to the invention comprises substrate layers infiltrated by a hardened material. The 3D object is fabricated by a method comprising the following steps: Position powder on all or part of a substrate layer. Repeat this step for the remaining substrate layers. Stack the substrate layers. Transform the powder into a substance that flows and subsequently hardens into the hardened material. The hardened material solidifies in a spatial pattern that infiltrates positive regions in the substrate layers and does not infiltrate negative regions in the substrate layers. In a preferred embodiment, the substrate is carbon fiber and excess substrate is removed by abrasion.
    Type: Application
    Filed: July 30, 2020
    Publication date: February 18, 2021
    Applicant: Impossible Objects LLC
    Inventors: Robert Swartz, Buckley Crist, Eugene Gore, Joseph M. Jacobson
  • Publication number: 20200384727
    Abstract: A 3D object according to the invention comprises substrate layers infiltrated by a hardened material. The 3D object is fabricated by a method comprising the following steps: Position powder on all or part of a substrate layer. Repeat this step for the remaining substrate layers. Stack the substrate layers. Transform the powder into a substance that flows and subsequently hardens into the hardened material. The hardened material solidifies in a spatial pattern that infiltrates positive regions in the substrate layers and does not infiltrate negative regions in the substrate layers. In a preferred embodiment, the substrate is carbon fiber and excess substrate is removed by abrasion.
    Type: Application
    Filed: February 10, 2020
    Publication date: December 10, 2020
    Applicant: Impossible Objects LLC
    Inventors: Robert Swartz, Buckley Crist, Eugene Gore, Joseph M. Jacobson
  • Publication number: 20200332271
    Abstract: Engineered Streptococcus canis Cas9 (ScCas9) variants include an ScCas9 protein with its PID being the PID amino acid composition of Streptococcus pyogenes Cas9 (SpCas9)-NG, an ScCas9 protein having a threonine-to-lysine substitution mutation at position 1227 in its amino acid sequence (Sc+), and an ScCas9 protein having a threonine-to-lysine substitution mutation at position 1227 and a substitution of residues ADKKLRKRSGKLATE in position 365-379 in the ScCas9 open reading frame (Sc++). Also included are CRISPR-associated DNA endonucleases with a PAM specificity of 5?-NG-3? or 5?-NNG-3? and a method of altering expression of a gene product by utilizing the engineered ScCas9 variants.
    Type: Application
    Filed: November 19, 2019
    Publication date: October 22, 2020
    Applicant: Massachusetts Institute of Technology
    Inventors: Pranam Chatterjee, Noah Michael Jakimo, Joseph M. Jacobson
  • Publication number: 20200048658
    Abstract: Population-Hastened Assembly Genetic Engineering is a method for continuous genome recoding using a mixed population of cells. Nucleic acid donors are distributed amongst a population of cells that continuously transfer nucleic acids to achieve asynchronous recoding of genetic information within a subpopulation of the cells. Recombination is achieved with biochemical systems compatible with virtually any organism. An engineered directed endonuclease comprises a nucleic acid recognition domain, a nucleic acid endonuclease domain, and a linker fusing or causing interaction between the nucleic acid recognition domain and the nucleic acid endonuclease domain. The method includes causing at least one engineered directed endonuclease to create a nick in a nucleic acid strand, the nick being offset from the recognition sequence of the nucleic acid recognition domain; causing homologous recombination of the strand with a donor nucleotide to create a modified genome; and replicating the modified genome.
    Type: Application
    Filed: June 17, 2019
    Publication date: February 13, 2020
    Applicant: Massachusetts Institute of Technology
    Inventors: Joseph M. Jacobson, Noah Jakimo, Lisa Nip
  • Publication number: 20190366626
    Abstract: A 3D object according to the invention comprises substrate layers infiltrated by hardened material. The 3D object is fabricated by a method comprising the following steps: Position powder on all or part of a substrate layer. Repeat this step for the remaining substrate layers. Stack the substrate layers. Transform the powder into a substance that flows and subsequently hardens into the hardened material. The hardened material solidifies in a spatial pattern that infiltrates positive regions in the substrate layers and does not infiltrate negative regions in the substrate layers. In a preferred embodiment, the substrate is carbon fiber and excess substrate is removed by abrasion.
    Type: Application
    Filed: August 13, 2019
    Publication date: December 5, 2019
    Applicant: Impossible Objects, Inc.
    Inventors: Robert Swartz, Buckley Crist, Eugene Gore, Joseph M. Jacobson
  • Patent number: 10377106
    Abstract: A 3D object according to the invention involves substrate layers infiltrated by a hardened material. The 3D object may be fabricated by a method comprising the following steps: Flatten a substrate layer. Position powder on all or part of a substrate layer. Repeat this step for the remaining substrate layers. Stack the substrate layers. Transform the powder into a substance that flows and subsequently hardens into the hardened material. The hardened material solidifies in a spatial pattern that infiltrates positive regions in the substrate layers and does not infiltrate negative regions in the substrate layers. In a preferred embodiment, the substrate is carbon fiber and excess substrate is removed by abrasion. Flattening a substrate layer involves reducing planar inconsistencies or imperfections, and comprises applying heat to each substrate layer, cooling the substrate layers, and optionally applying tension and/or pressure to the heated and cooled substrate layers.
    Type: Grant
    Filed: October 2, 2017
    Date of Patent: August 13, 2019
    Assignee: Impossible Objects, Inc.
    Inventors: Robert Swartz, Buckley Crist, Eugene Gore, Joseph M. Jacobson
  • Patent number: 10377080
    Abstract: A 3D object according to the invention comprises substrate layers infiltrated by a hardened material. The 3D object is fabricated by a method comprising the following steps: Position powder on all or part of a substrate layer. Repeat this step for the remaining substrate layers. Stack the substrate layers. Transform the powder into a substance that flows and subsequently hardens into the hardened material. The hardened material solidifies in a spatial pattern that infiltrates positive regions in the substrate layers and does not infiltrate negative regions in the substrate layers. In a preferred embodiment, the substrate is carbon fiber and excess substrate is removed by abrasion.
    Type: Grant
    Filed: November 3, 2017
    Date of Patent: August 13, 2019
    Assignee: Impossible Objects, Inc.
    Inventors: Robert Swartz, Buckley Crist, Eugene Gore, Joseph M. Jacobson
  • Publication number: 20190218532
    Abstract: A Streptococcus canis Cas9 (ScCas9) ortholog and its engineered variants, possessing novel PAM specificity, is an addition to the family of CRISPR-Cas9 systems. ScCas9 endonuclease is used in complex with guide RNA, consisting of identical non-target-specific sequence to that of the guide RNA SpCas9, for specific recognition and activity on a DNA target immediately upstream of either an “NNGT” or “NNNGT” PAM sequence. A novel DNA-interacting loop domain within ScCas9, and other Cas9 orthologs, such as those from Streptococcus gordonii and Streptococcus angionosis facilitates a divergent PAM sequence from the “NGG” PAM of SpCas9.
    Type: Application
    Filed: September 19, 2018
    Publication date: July 18, 2019
    Applicant: Massachusetts Institute of Technology
    Inventors: Joseph M. Jacobson, Noah Michael Jakimo, Pranam Chatterjee
  • Publication number: 20180298391
    Abstract: A self-reconfiguring genome uses a cassette having operons or DNA sequences that code for guide RNA, reverse transcriptase, donor RNA, and a CRISPR cleavage enzyme. A self-reconfiguring genome may be based on lambda recombineering of in situ generated oligonucleotides. A method for programmable self-modification of a cellular genome includes transcribing guide RNA from a self-reconfiguring cassette, associating the transcribed guideRNA with the CRISPR enzyme, intercalcating a region of complimentary sequence within an integration site of the genome, cutting upstream of a PAM site within the integration site; transcribing the donorRNA, translating donorRNA to double-stranded DNA, and recombining the double-stranded DNA via homologous recombination at the cut site of the integration site.
    Type: Application
    Filed: February 26, 2018
    Publication date: October 18, 2018
    Applicant: Massachusetts Institute of Technology
    Inventors: Noah Jakimo, Peter A. Carr, Joseph M. Jacobson
  • Publication number: 20180282722
    Abstract: A chimeric DNA:RNA guide for very high accuracy Cas9 genome editing employs nucleotide-type substitutions in nucleic acid-guided endonucleases for enhanced specificity. The CRISPR-Cas9 gene editing system is manipulated to generate chimeric DNA:RNA guide strands to minimize the off-target cleavage events of the S. pyogenes Cas9 endonuclease. A DNA:RNA chimeric guide strand is sufficient to guide Cas9 to a specified target sequence for indel formation and minimize off-target cleavage events due to the specificity conferred by DNA-DNA interactions. Use of chimeric mismatch-evading lowered-thermostability guides (“melt-guides”) demonstrate that nucleotide-type substitutions in the spacer can reduce cleavage of sequences mismatched by as few as a single base pair. The chimeric mismatch-evading lowered-thermostability guides replace most gRNA spacer positions with DNA bases to suppress mismatched targets under Cas9's catalytic threshold.
    Type: Application
    Filed: November 21, 2017
    Publication date: October 4, 2018
    Applicant: Massachusetts Institute of Technology
    Inventors: Noah Jakimo, Pranam Chatterjee, Joseph M. Jacobson
  • Patent number: 10030253
    Abstract: A method for synthesizing long DNA constructs from oligonucleotide precursors directly within a microfluidic device uses several oligonucleotides at once. A precursor mix containing at least two oligonucleotide precursors with at least partial base complementarity is introduced into an input of a microfluidic chip and at least one cycle of at least one gene synthesis protocol is applied to fabricate a DNA construct containing the sequence of at least two oligonucleotide precursors. A method for the synthesis of a modified DNA construct includes electroporating at least one oligonucleotide encoding for at least one point mutation and having homology with at least one DNA region of a target cell into the target cell and incorporating the oligonucleotide into the target cell DNA through the action of recombination protein beta or a recombination protein beta functional homolog.
    Type: Grant
    Filed: October 30, 2014
    Date of Patent: July 24, 2018
    Assignee: Massachusetts Institute of Technology
    Inventors: David Kong, Peter A. Carr, Joseph M. Jacobson
  • Publication number: 20180141305
    Abstract: A 3D object according to the invention comprises substrate layers infiltrated by a hardened material. The 3D object is fabricated by a method comprising the following steps: Position powder on all or part of a substrate layer. Repeat this step for the remaining substrate layers. Stack the substrate layers. Transform the powder into a substance that flows and subsequently hardens into the hardened material. The hardened material solidifies in a spatial pattern that infiltrates positive regions in the substrate layers and does not infiltrate negative regions in the substrate layers. In a preferred embodiment, the substrate is carbon fiber and excess substrate is removed by abrasion.
    Type: Application
    Filed: August 25, 2015
    Publication date: May 24, 2018
    Applicant: IMPOSSIBLE OBJECTS LLC
    Inventors: Robert Swartz, Buckley Crist, Eugene Gore, Joseph M. Jacobson