September 2020 patents
Innovations in enrichment of cells, fluorination of organic compounds, fabrication of nanopores, differentiation of stem cells, soft robotics, and more
Harvard faculty David Mooney, Daniel Branton, Marc Kirschner, George Church, Robert Wood, Jennifer Lewis, and Conor Walsh are among the inventors issued U.S. patents in September 2020.
The innovations recognized are as follows:
Compositions and methods for enrichment of cells
U.S. Patent 10,758,573 (September 1, 2020)
Pascal Joly, Georg N. Duda, Thomas Schaus, Anke Dienelt, Andrea Sass, David J. Mooney
Abstract: The present invention is directed to a device for enriching cells with a cell surface marker, comprising an aptamer suitable for specifically binding the cell surface marker, and beads coupled thereto, wherein the aptamer is coupled to the beads in a manner that allows for release of cells expressing the cell surface marker, in the absence of a chemical agent, and production of a cell population enriched for cells expressing the cell surface marker, substantially free of beads and aptamer. Kits comprising the device or components thereof, and methods of cell enrichment, are also provided. In exemplary embodiments, the device contains an aptamer that specifically binds CD31.
Fluorination of organic compounds
U.S. Patent 10,759,764 (September 1, 2020)
Tobias Ritter and Constanze Nicole Neumann
Abstract: Methods for fluorinating organic compounds utilizing a novel organic reagent are described herein. The invention further discloses the utility of this reagent for incorporation of the 18 F isotope into hydroxyl group-containing organic molecules for PET imaging studies. Preparation of the reagents is described along with isolable intermediate structures from reaction of the reagent with a hydroxyl group-containing organic molecule.
Controlled fabrication of nanopores in nanometric solid state materials
U.S. Patent 10,766,762 (September 8, 2020)
Christopher John Russo, Jene A. Golovchenko, and Daniel Branton
Abstract: There is provided a nanometric structure that includes a self-supporting nanometric material having a thickness of no more than about 5 nm. A plurality of nanopores is provided in the nanometric material, and the nanopore plurality has a density of at least about 1000 nanopores/cm2. Each nanopore in the plurality of nanopores has a diameter that is no greater than about 10 nm. The plurality of nanopores is monodisperse in diameter with a variation of about ±30%. In a further nanometric structure provided herein there is included a self-supporting nanometric material having a thickness of no more than about 5 nm. A plurality of nanopores in the nanometric material includes at least about 50 nanopores. Each nanopore in the plurality of nanopores has a diameter that is no greater than about 10 nm. The plurality of nanopores is monodisperse in diameter with a variation of about ±30%.
Methods for differentiation
U.S. Patent 10,767,162 (September 8, 2020)
Victor Chun Li, Marc W. Kirschner
Abstract: Described herein are methods relating to the differentiation of stem cells to more differentiated phenotypes, e.g. to terminally differentiated cell types and/or precursors thereof. In some embodiments, the methods relate to contacting the stem cells with differentiation factors and halting the cell cycle, thereby increasing the rate of differentiation.
RNA-guided transcriptional regulation
U.S. Patent 10,767,194 (September 8, 2020)
George M. Church, Prashant G. Mali, and Kevin M. Esvelt
Abstract: Methods of modulating expression of a target nucleic acid in a cell are provided including introducing into the cell a first foreign nucleic acid encoding one or more RNAs complementary to DNA, wherein the DNA includes the target nucleic acid, introducing into the cell a second foreign nucleic acid encoding a nuclease-null Cas9 protein that binds to the DNA and is guided by the one or more RNAs, introducing into the cell a third foreign nucleic acid encoding a transcriptional regulator protein or domain, wherein the one or more RNAs, the nuclease-null Cas9 protein, and the transcriptional regulator protein or domain are expressed, wherein the one or more RNAs, the nuclease-null Cas9 protein and the transcriptional regulator protein or domain co-localize to the DNA and wherein the transcriptional regulator protein or domain regulates expression of the target nucleic acid.
Method of making polynucleotides using closed-loop verification
U.S. Patent 10,774,366 (September 15, 2020)
George M. Church, Kettner John Frederick Griswold, Jr.
Abstract: A method for making a polynucleotide is provided including (a) delivering one or more reaction reagents including an error prone or template independent DNA polymerase, cations and a selected nucleotide to a reaction site including an initiator sequence having a terminal nucleotide for a time period and under conditions capable of covalently adding one or more of the selected nucleotide to the terminal nucleotide at the 3' end of the initiator such that the selected nucleotide becomes a terminal nucleotide, and (b) determining whether the selected nucleotide has been added to the terminal nucleotide, wherein if the selected nucleotide has not been added to the terminal nucleotide, then repeating step (a) until the selected nucleotide has been added, and (c) repeating steps (a) and (b) until the polynucleotide is formed.
Reduced and oxidized polysaccharides and methods of use thereof
U.S. Patent 10,780,171 (September 22, 2020)
David J. Mooney, Alexander Stafford, Rajiv Desai, Kathleen Martinick
Abstract: The present invention is directed to reduced and highly oxidized polysaccharides, such as alginates, that are useful for encapsulating therapeutic or diagnostic agents, or lipid based nanoparticles, e.g., liposomes or virosomes, encapsulating therapeutic or diagnostic agents, prior to their delivery into a subject, as well as methods for making and using them.
Soft robotic actuators and grippers
U.S. Patent 10,780,591 (September 22, 2020)
Kevin C. Galloway, Robert J. Wood, and Kaitlyn Becker
Abstract: A method of making an actuator having a complex internal shape includes providing a core of a shape that defines an internal cavity of an actuator; molding an actuator around the core, wherein the core occupies the internal cavity of the actuator, the cavity having an opening; generating a pressure differential between an exterior surface of the actuator and the internal cavity of the actuator, wherein the external pressure is less than the internal pressure, to expand the actuator cavity; and removing the core through the opening of the expanded actuator cavity.
Artificial tympanic membrane devices and uses
U.S. Patent 10,786,349 (September 29, 2020)
Aaron K. Remenschneider, Elliot Kozin, Nicole Black, Michael J. McKenna, Daniel J. Lee, Jennifer Lewis, John Rosowski, David Kolesky, Mark A. Skylar-Scott, and Alexander D. Valentine
Abstract: This disclosure features artificial tympanic membrane graft devices and two-component bilayer graft devices that include a scaffold having a plurality of ribs made of a first material and a plurality of spaces between the ribs filled or made with the first material, a different, second material, a combination of the first and a second materials, or a combination of a second material and one or more other different materials. The bilayer graft devices have two components or layers. One component, e.g., the underlay graft device, can include a projection, and the second component, e.g., the overlay graft device, can include an opening that corresponds to the projection (or vice versa) so that the opening and the projection can secure the two layers together in a "lock and key" manner. This disclosure also features methods of making, using, and implanting the three-dimensional artificial tympanic membrane and bilayer graft devices.
Large gene excision and insertion
U.S. Patent 10,787,684 (September 29, 2020)
Susan M. Byrne and George M. Church
Abstract: Methods of simultaneously excising large nucleic acid sequences from a target nucleic acid and inserting large foreign nucleic sequences into the target nucleic acid sequence using DNA binding protein nucleases are described.
Multi-segment reinforced actuators and applications
U.S. Patent 10,788,058 (September 29, 2020)
Kevin Galloway, Conor Walsh, Donal Holland, Panagiotis Polygerinos, Tyler Clites, Paxton Maeder-York, Ryan Neff, Emily Marie Boggs, and Zivthan Dubrovsky
Abstract: A multi-segment reinforced actuator includes (a) a soft actuator body that defines a chamber and (b) a plurality of distinct reinforcement structures on or in respective segments of the soft actuator body. First and second reinforcement structures are respectively configured to produce a first and second actuation motions, respectively, in first and second segments of the soft actuator body when fluid flows into or out of the chamber. The actuation motions are selected bending, extending, expansion, contraction, twisting, and combinations thereof; and the first actuation motion differs from the second actuation motion. The actuator can be used, e.g., to facilitate bending of the thumb with corresponding bending, extending, expansion, contraction, and twisting actuation motions.