Abstract: Provided herein are 2?-O-methyl 3?phosphorothioate (MS)-modified synthetic nucleic acid molecules (single guide RNAs (sgRNAs)) for the use with a Cas9 nuclease in combination as a ribonucleoprotein (RNP) complex for an electroporation-based ex vivo targeted gene disruption of the BCL11A erythroid enhancer's +55, +58, or +62, functional regions. Additionally, provided herein are said RNP complexes (Cas9:MS-sgRNA), and compositions comprising the modified synthetic nucleic acid molecules or said RNP complexes, 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.
Type:
Grant
Filed:
May 25, 2018
Date of Patent:
October 17, 2023
Assignee:
THE CHILDREN'S MEDICAL CENTER CORPORATION
Abstract: Embodiments disclosed here provide engineered modified hematopoietic stem cells (HSCs), artificially prostaglandin E2 (PGE2)-stimulated HSCs, compositions comprising these HSCs, methods of using these modified HSCs for treating autoimmune diseases and disorders and for suppressing the immune system. In particular, the engineered modified HSCs or PGE2-stimulated HSCs express the surface marker, programmed cell death-1 ligand 1 (PD-L1).
Type:
Application
Filed:
March 15, 2023
Publication date:
October 12, 2023
Applicant:
THE CHILDREN'S MEDICAL CENTER CORPORATION
Abstract: The present invention is directed to purified preparations of dermal mesenchymal stem cells that are characterized by the cell surface expression of the ABCB5 P-glycoprotein. The cells may be used for any purpose that mesenchymal stem cells from other course are used. For instance they may be administered to treat an organ transplant recipient to improve allograft survival or as a treatment to patients with autoimmune diseases such as multiple sclerosis and rheumatoid arthritis.
Abstract: Described herein are compositions (e.g. cells and transgenic animals) and methods relating to engineered Ig loci that permit expression of particular antibodies or antibody segments while still permitting recombination and/or maturation process for antibody optimization.
Type:
Grant
Filed:
June 25, 2018
Date of Patent:
October 3, 2023
Assignee:
CHILDREN'S MEDICAL CENTER CORPORATION
Inventors:
Frederick W. Alt, Hwei-Ling Cheng, Ming Tian
Abstract: Provided herein, in some aspects, are polypeptide monomers comprising an angiotensin-converting enzyme 2 (ACE2) ectodomain and an oligomerization domain. Also provided herein are oligomeric complexes comprising ACE2 monomers. Methods of using such to monomers and oligomeric complexes for the diagnosis, prevention, and treatment of viral infections such as the coronavirus are also provided.
Type:
Grant
Filed:
May 19, 2021
Date of Patent:
October 3, 2023
Assignee:
Children's Medical Center Corporation
Inventors:
Bing Chen, Tianshu Xiao, Yongfei Cai, Jun Zhang
Abstract: Provided herein, in some aspects, are delivery vehicles comprising a ceramide and an agent to be delivered attached to the ceramide. In some embodiments, the ceramide does not comprise a fatty acid (i.e., is a sphingosine). In some embodiments, the ceramide comprises a fatty acid. In some embodiments, the ceramide is a glycoceramide. In some embodiments, the agent is attached to the ceramide covalently (e.g., via a linker). In some embodiments, the agent to be delivered is a therapeutic agent. The ceramide 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 ceramide 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 ceramide delivery vehicle are also provided.
Type:
Grant
Filed:
April 12, 2019
Date of Patent:
October 3, 2023
Assignee:
Children's Medical Center Corporation
Inventors:
Wayne I. Lencer, Daniel J F Chinnapen, Richard I. Duclos
Abstract: Described herein are methods and assays for detection of recombination and/or rearrangement events in a cell. In some embodiments, the methods and/or assays relate to Linear Amplification Mediated (LAM)-PCR. In some embodiments, the recombination event is a V(D)J recombination event.
Type:
Application
Filed:
March 31, 2023
Publication date:
September 21, 2023
Applicant:
THE CHILDREN'S MEDICAL CENTER CORPORATION
Inventors:
Frederick W. ALT, Jiazhi HU, Sherry LIN, Zhou DU, Yu ZHANG, Huan CHEN
Abstract: The disclosure provides compositions comprising exosome subpopulations, and methods of their use in subjects having certain disorders including lung disorders, cardiovascular disorders, renal disorders and ischemic neural disorders.
Type:
Grant
Filed:
March 10, 2020
Date of Patent:
September 19, 2023
Assignee:
Children's Medical Center Corporation
Inventors:
S. Alexander Mitsialis, Stella Kourembanas, Konstantinos Sdrimas
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: Techniques disclosed herein provide a method of informing blood product administration to a perioperative patient. Some patients may be at risk of perioperative bleeding following a surgery, such as a cardiac surgery. As discussed herein, coagulation status of a patient is monitored perioperatively and at least one value indicative of the coagulation status may be used to determine the patient’s risk of perioperative bleeding. Should the patient’s risk of perioperative bleeding be determined to be sufficiently high, such as when the value(s) are below one or more thresholds, techniques disclosed herein may also in some embodiments aid in titration of a blood product to be administered to the perioperative patient to adjust the patient’s risk of bleeding.
Type:
Application
Filed:
July 8, 2021
Publication date:
September 7, 2023
Applicant:
CHILDREN'S MEDICAL CENTER CORPORATION
Inventors:
Sitaram Emani, Sirisha Emani, Juan C. lbla, Meena Nathan, Vishnu Sankar Emani
Abstract: The various examples of the present disclosure are directed towards systems and methods for diagnosing brain health. An exemplary system includes a microscope, a processor, and a memory. The microscope outputs image data of a cornea of a patient. The memory has a plurality of stored code sections, which, when executed by the processor, include instructions for analyzing cornea image data to determine brain health. The instructions begin with receiving cornea image data from the microscope. The instructions then provide for determining at least one marker from the received cornea image data. The instructions then provide for outputting a brain health diagnosis based on the at least one marker.
Type:
Grant
Filed:
September 11, 2020
Date of Patent:
September 5, 2023
Assignee:
THE CHILDREN'S MEDICAL CENTER CORPORATION
Abstract: Antibodies, and antigen-binding fragments thereof, that specifically bind to Cluster of Differentiation 1a (CD1a) are provided. Embodiments include uses, and associated methods of using the antibodies, and antigen-binding fragments thereof.
Type:
Grant
Filed:
October 7, 2021
Date of Patent:
September 5, 2023
Assignees:
Pfizer Inc., Children's Medical Center Corporation
Inventors:
Florian Winau, Oleg V. Kovalenko, Chew Shun Chang, Di Wu, Nicholas Andrew Marze, Shian-Huey Chiang
Abstract: The present disclosure provides compositions and methods for delivery of therapeutic agents across a barrier. The compositions include a therapeutic agent (e.g., antimicrobial agent, antibiotic), a permeation enhancer comprising sodium dodecyl sulfate, limonene, and/or bupivacaine which increases the flux of the therapeutic agent across the barrier, and a matrix forming agent that is a poloxamer (e.g., poloxamer P188), wherein the composition comprises: between about 0.2% and 3.2% wt/vol of a permeation enhancer that is sodium dodecyl sulfate; when present, between about 0.2% and 2.0% wt/vol of a permeation enhancer that is bupivacaine; between about 0.5% and 7.0% wt/vol of a permeation enhancer that is limonene; between approximately 18-62% P188; and the composition forms a gel at temperatures above a phase transition temperature that is less than about 37° C. The matrix forming agent forms a gel at a suitable gelation temperature and rheological properties for use in drug delivery.
Abstract: Embodiments herein provide specially designed synthetic BCL11A-targeting microRNAs for RNA polymerase II expression, and methods of use to treat hemoglobinopathies such as sickle cell disease or thalassemia by increasing the expression levels of fetal hemoglobin levels.
Type:
Grant
Filed:
August 17, 2021
Date of Patent:
August 29, 2023
Assignee:
THE CHILDREN'S MEDICAL CENTER CORPORATION
Inventors:
Michael Milsom, David A. Williams, Richard Gregory
Abstract: Provided herein, in some aspects, are compositions comprising vasoocclusion-inhibiting agents encapsulated in RBCs and uses thereof for treating blood vessel occlusion (e.g., in Sickle Cell Disease).
Type:
Application
Filed:
July 9, 2021
Publication date:
August 24, 2023
Applicant:
Children's Medical Center Corporation
Inventors:
Shin-Young Park, Leslie E. Silberstein, Jina Ryu, Min Liu
Abstract: Provided herein are materials and methods for efficiently delivering nucleic acids to cochlear and vestibular cells, and methods of treating sensory transduction disorders associated with a genetic defect. Some embodiments are directed to a synthetic inner ear hair cell targeting adeno-associated virus (AAV) vector, a cell comprising the synthetic inner ear hair cell targeting AAV vector, and method of treating Usher Syndrome in a subject using the synthetic inner ear hair cell targeting AAV vector.
Abstract: The present disclosure relates to compositions and methods for treating Williams syndrome (WS), herein identified as a neurodevelopmental oligodendrocyte hypomyelination-associated disease, and to compositions and methods for treatment of other neurodevelopmental myelination abnormality diseases or disorders.
Type:
Grant
Filed:
December 21, 2018
Date of Patent:
August 22, 2023
Assignees:
Children's Medical Center Corporation, Massachusetts Institute of Technology
Abstract: Provided herein are imidazopyrimidine compounds, such as compounds of Formula (I), for use in enhancing human immune response and/or as adjuvants in vaccines.
Type:
Grant
Filed:
November 14, 2018
Date of Patent:
August 22, 2023
Assignees:
Children's Medical Center Corporation, Dana-Farber Cancer Institute, Inc.
Inventors:
Ofer Levy, David J. Dowling, Francesco Borriello, David A. Scott, Spencer E. Brightman, Frederic Feru
Abstract: Provided herein are methods and compositions related to treating a hemoglobinopathy. Also provided herein a gene therapeutics for the treatment of hemoglobinopathies and the induction of fetal hemoglobin (HbF).
Type:
Application
Filed:
July 19, 2021
Publication date:
August 17, 2023
Applicant:
The Children's Medical Center Corporation