Abstract: Disclosed herein are polypeptides and fusion polypeptides that have anti-angiogenic activity that can be used to inhibit tumor growth and tumor metastasis. The polypeptide consists of 9 or less consecutive amino acid residues (e.g., 8, 7, 6, 5, or 4) comprising the active core amino acid sequence DWLP, or an amino acid substitution variant thereof. Specific amino acid substitutions are disclosed herein. In some embodiments, the peptide consists essentially of 4-6 mers identified as exhibiting the activity of prosaposin A. Also disclosed herein are therapeutic compositions comprising the polypeptides and fusion polypeptides, and their use in the treatment, prevention, and inhibition of angiogenesis-related diseases and disorders such as cancer and cancer metastasis.
Abstract: The present application is generally directed to novel pneumococcal polypeptide antigens and nucleic acids encoding such antigens, and immunogenic compositions comprising such antigens for treating and preventing pneumococcal infection. The present invention further provides method of using the antigens to elicits an immune response (e.g., IL-17A response, a T cell-mediated and/or B-cell-mediated immune responses). The present invention also provides methods of prophylaxis and/or treatment of pneumococcal-mediated diseases, such as sepsis, comprising administering an immunogenic composition including one or more of a combination of pneumococcal antigens or functional fragments thereof as disclosed herein. In some embodiments, one or more pneumococcal antigens can be present in a polysaccharide conjugate. The compositions induce an anti-pneumococcus immune response when administered to a mammal.
Abstract: The invention provides compositions comprising nucleic acid complexes for use in screening compounds based on their ability to modulate binding interactions, wherein the compounds are barcoded.
Abstract: Method and devices for viewing one or more valve leaflets via a viewer. In some embodiments the viewer includes a body having a first end and a second end opposite the first end, the first end being closed and having a transparent viewing window, the second end arranged to be attached to an aorta or a pulmonary artery, and one or more ports arranged to provide fluid access to an internal portion of the viewer to pressurize the one or more leaflets. A diameter of the viewing window is larger than an outer diameter of the second end. An outer diameter of the first end of the body is larger than an outer diameter of the second end. The body is a tubular body.
Type:
Application
Filed:
January 22, 2021
Publication date:
February 9, 2023
Applicant:
Children's Medical Center Corporation
Inventors:
Peter E. Hammer, Ignacio Berra, David Hoganson, Pedro J. del Nido, Douglas P. Perrin
Abstract: Provided herein are nucleic acid molecules that target the BCL11A enhancer functional regions, compositions comprising the nucleic acid molecules and methods for increasing fetal hemoglobin levels in a cell by disrupting BCL11A expression at the genomic level. Also provided herein are methods and compositions relating to the treatment of hemoglobinopathies by reinduction of fetal hemoglobin levels. In particular, the nucleic acid molecules target the +62, +58, and/or the +55 enhancer functional regions.
Type:
Grant
Filed:
May 6, 2016
Date of Patent:
February 7, 2023
Assignees:
THE CHILDREN'S MEDICAL CENTER. CORPORATION, THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY
Inventors:
Daniel E. Bauer, Stuart H. Orkin, Neville Sanjana, Ophir Shalem, Feng Zhang
Abstract: Embodiments herein relate to in vitro production methods of hematopoietic stem cell (HSC) and hematopoietic stem and progenitor cell (HSPC) that have long-term multilineage hematopoiesis potentials upon in vivo engraftment. The HSC and HSPCs are derived from pluripotent stem cells-derived hemogenic endothelia cells (HE) by non-integrative episomal vectors-based gene transfer.
Type:
Grant
Filed:
June 14, 2018
Date of Patent:
February 7, 2023
Assignee:
THE CHILDREN'S MEDICAL CENTER CORPORATION
Abstract: The present invention provides compositions and methods for treating a myopathy. In certain embodiments, the invention provides compositions and methods for treating, improving muscle function, and prolonging survival in a subject with X-linked myotubular myopathy (XLMTM). The present invention provides a method comprising systemic administration of a composition that induces the increased expression of myotubularin in the muscle of a subject. The invention provides sustained regional and global increases in muscle function.
Type:
Grant
Filed:
December 28, 2017
Date of Patent:
January 31, 2023
Assignees:
Wake Forest University Health Sciences, Genethon, Children's Medical Center Corporation
Inventors:
Martin K. Childers, Alan H. Beggs, Ana Maria Buj Bello
Abstract: An apparatus for generating a prediction that a patient will experience a seizure by monitoring a patient's body temperature over time is provided. The apparatus may include a sensor to sense temperature. The apparatus may monitor, using the sensor, the body temperature of the patient and compare the body temperature over a first period of time and a second period of time. The apparatus may generate a prediction of whether the patient will experience a seizure following the second period of time based at least in part on a result of the comparing.
Abstract: The disclosure provides modified biotin-binding proteins which can be expressed in soluble form in high yield in bacteria. Also provided are fusion proteins comprising the modified biotin-binding protein and an antigen. The disclosure further provides non-hemolytic variants of alpha-hemolysin from S. aureus and fusion protein comprising non-hemolytic variant of alpha-hemolysin and a biotin-binding domains. Immunogenic compositions comprising the proteins are also disclosed and use of such immunogenic compositions for inducing an immune response or for vaccinating a subject are also disclosed.
Abstract: Provided herein, in some aspects, are delivery vehicles comprising a glycosphingolipid and an agent to be delivered attached to the glycosphingolipid. In some embodiments, the glycosphingolipid comprises an oligosaccharide and a short chain (e.g., C0-C3) ceramide. In some embodiments, the agent to be delivered is a therapeutic agent. The glycosphingolipid is able to deliver the agent to a cell or to a cellular compartment, as well as across the musical barrier. In some embodiments, agents delivered using the glycosphingolipid described herein exhibit longer half-life, compared to agents delivered alone. Methods of delivering a therapeutic agent to a subject for treating a disease using the glycosphingolipid delivery vehicle are also provided.
Abstract: The present invention generally relates to particles such as nanoparticles and, in particular, to targeted nanoparticles. In some cases, the particles may have a targeting moiety that is inhibited from recognizing a target, for example, by being positioned within the particle at an internal location. The application of a stimulus, such as light, may allow the targeting moiety to interact externally of the particle. Accordingly, the particles may be targeted to specific locations using the application of a suitable stimulus. For instance, in one embodiment, particles containing cell-penetrating peptides attached via a first attachment and a second attachment containing a photocleavable entity may be administered to a subject, and light may be applied, e.g., to the eye, to cleave the photocleavable entity. However, despite the cleavage, the peptides remain associated with the particle via the first attachment, and thus, the particles may be able to penetrate cells within the eye due to peptides.
Abstract: The present invention provides methods and compostions to improve the efficiency of somatic cell nuclear transfer (SCNT) and the consequent production of nuclear transfer ESC (ntESC) and transgenic cells and/or non-human animals. More specifically, the present invention relates to the discovery that trimethylation of Histone H3-Lysine 9 (H3K9me3) in reprogramming resistant regions (RRRs) in the nuclear genetic material of donor somatic cells prevents efficient somatic cell nuclear reprogramming or SCNT. The present invention provide methods and compositions to decrease H3K9me3 in methods to improve efficacy of SCNT by exogenous or overexpression of the demethylase Kdm4 family and/or inhibiting methylation of H3K9me3 by inhibiting the histone methyltransferases Suv39h1 and/or Suv39h2.
Abstract: Provided herein are method of treating cancer using agents that inhibit the interaction between Methyltransferase like 3 (METTL3) and Eukaryotic Translation Initiation Factor 3 Subunit H (EIF3h), and optionally agents that inhibit Bromodomain-containing protein 4 (BRD4). The present disclosure demonstrates the topology of individual polyribosomes with single METTL3 foci found in close proximity to 5? cap-binding proteins, revealing a previously unknown direct physical and functional interaction between METTL3 and the eukaryotic translation initiation factor 3 subunit h (eIF3h).
Abstract: Provided herein are isolated anaplastic lymphoma kinase (ALK) peptides that are fragments of the cytoplasmic portion of an ALK protein shared by cancers having an ALK rearrangement and cancers expressing the ALK protein, that bind a human leukocyte antigen (HLA), and elicit an immune response against one or more ALK-positive cancers. Also provided are isolated ALK peptides that are modified with an amphiphilic conjugate to increase T-cell expansion and greatly enhance anti-tumor efficacy. The invention also provides polynucleotides encoding isolated ALK peptides, vaccines comprising an isolated ALK peptide or polynucleotide, immunogenic compositions thereof, and kits for administering the same. Methods of treatment and methods of generating an immune response in a subject by administering the ALK-specific peptide antigens, immunogens, vaccines, or immunogenic compositions thereof are provided.
Abstract: A device and method for detecting and recording animal behavior is provided. The device includes an enclosure having first and second chambers, each of the chambers having exterior panels formed of an opaque material, at least one image capture device disposed in each of the first and second chambers, the at least one image capture device arranged to capture behavior data of one or more freely roaming rodents, and a first container insertable into one of the first and second containers and positioned below a respective image capture device, the container having one or more corrals into which one or more rodents are housed during testing, the container being formed of a transparent material. In some embodiments, the first container is formed of a red transparent material, the one or more rodents being unable to see through the red transparent material.
Abstract: Methods, systems, and coaptation measurement devices as described herein include an elongate sensor body at the end of a proximal connecting member, and a plurality of sensors in an array across a face of the sensor body, wherein each sensor of the plurality of sensors is configured to detect if a portion of a heart valve is in contact with the sensor.
Abstract: The present invention provides compositions and systems for delivery of nanocarriers to cells of the immune system. The invention provides vaccine nanocarriers capable of stimulating an immune response in T cells and/or in B cells, in some embodiments, comprising at least one immunomodulatory agent, and optionally comprising at least one targeting moiety and optionally at least one immunostimulatory agent. The invention provides pharmaceutical compositions comprising inventive vaccine nanocarriers. The present invention provides methods of designing, manufacturing, and using inventive vaccine nanocarriers and pharmaceutical compositions thereof. The invention provides methods of prophylaxis and/or treatment of diseases, disorders, and conditions comprising administering at least one inventive vaccine nanocarrier to a subject in need thereof.
Type:
Grant
Filed:
August 19, 2019
Date of Patent:
January 10, 2023
Assignees:
MASSACHUSETTS INSTITUTE OF TECHNOLOGY, THE BRIGHAM AND WOMEN'S HOSPITAL, INC., PRESIDENT AND FELLOWS OF HARVARD COLLEGE, THE CHILDREN'S MEDICAL CENTER CORPORATION
Inventors:
Ulrich H. von Andrian, Omid C. Farokhzad, Robert S. Langer, Tobias Junt, Elliott Ashley Moseman, Liangfang Zhang, Pamela Basto, Matteo Iannacone, Frank Alexis
Abstract: An optical bulb for a medical device includes first and second bodies. The first body has a substantially hemispherical distal side. The second body extends from the first body and includes a mechanical connection point at or near the proximal side of the second body. An instrument channel extends through the optical bulb from the proximal side of the second body to the distal side of the first body. An imaging channel extends an aperture defined in the proximal side of the second body and terminates between the proximal and substantially hemispherical distal sides of the first body. The distal end of the imaging channel is substantially hemispherical. The first body is configured and arranged to provide a substantially uniform image path within a field of view of a camera disposed in the imaging channel.
Type:
Grant
Filed:
March 9, 2018
Date of Patent:
January 10, 2023
Assignee:
The Children's Medical Center Corporation
Inventors:
Anthony Maiorano, Jeffrey C. Cerier, Benjamin D. Masella, David P. Biss, Brian E. MacMillin
Abstract: The present invention provides compositions and methods for the treatment or prevention of a lysosomal disease or disorder involving increasing the level, expression, or activity of a metallothionein polypeptide or polynucleotide in the subject.
Type:
Grant
Filed:
January 16, 2018
Date of Patent:
January 10, 2023
Assignees:
CHILDREN'S MEDICAL CENTER CORPORATION, OSPEDALE SAN RAFFAELE S.R.L., DANA-FARBER CANCER INSTITUTE, INC., FONDAZIONE TELETHON
Abstract: Described herein are methods and compositions for treating or preventing an allergy or anaphylaxis. Certain aspects of the invention relate to administering to a subject an agent that inhibits RELM?.
Type:
Application
Filed:
February 23, 2021
Publication date:
January 5, 2023
Applicant:
THE CHILDREN'S MEDICAL CENTER CORPORATION
Inventors:
Talal Amine Chatila, Elena Crestani, Emmanuel Stephen Victor, Azza Abdel-Gadir, Rima Rachid