Harvard faculty Charlie Lieber, Arlene Sharpe, Chao-ting Wu, Dave Weitz, Eric Mazur, George Church, Conor Walsh, Rob Wood, Charles Richardson, Wendy Garrett, Joost Vlassak, Zhigang Suo, David Mooney, Joanna Aizenberg, George Whitesides, Gary King, Yoshito Kishi, Adam Cohen, David Liu, and Roy Gordon are among the inventors issued U.S. patents in August 2019.

The innovations recognized are as follows:

Scaffolds comprising nanoelectronic components for cells, tissues, and other applications
U.S. Patent 10,369,255 (August 6, 2019)

Charles M. Lieber, Jia Liu, Bozhi Tian, Tal Dvir, Robert S. Langer, and Daniel S. Kohane

Abstract: The present invention generally relates to nanoscale wires and tissue engineering. In various embodiments, cell scaffolds for growing cells or tissues can be formed that include nanoscale wires that can be connected to electronic circuits extending externally of the cell scaffold. The nanoscale wires may form an integral part of cells or tissues grown from the cell scaffold, and can even be determined or controlled, e.g., using various electronic circuits. This approach allows for the creation of fundamentally new types of functionalized cells and tissues, due to the high degree of electronic control offered by the nanoscale wires and electronic circuits. Accordingly, such cell scaffolds can be used to grow cells or tissues which can be determined and/or controlled at very high resolutions, due to the presence of the nanoscale wires, and such cell scaffolds will find use in a wide variety of novel applications, including applications in tissue engineering, prosthetics, pacemakers, implants, or the like.

Methods and compositions for the treatment of persistent infections and cancer by inhibiting the programmed cell death 1 (PD-1) pathway
U.S. Patent 10,370,446 (August 6, 2019)

Gordon Freeman, Arlene Sharpe, David M. Dorfman, Rafi Ahmed, Daniel Barber, and E. John Wherry

Abstract: The present invention provides methods and compositions for the treatment, prevention, or reduction of persistent infections, such as chronic infections, latent infections, and slow infections and cancer. The methods and compositions of the invention are also useful for the alleviation of one or more symptoms associated with such infections and cancer.

Endocrine precursor cells, pancreatic hormone-expressing cells and methods of production
U.S. Patent 10,370,645 (August 6, 2019)

Kevin A. D'Amour, Anne Bang, and Emmanuel E. Baetge

Abstract: Disclosed herein are cell cultures and enriched cell populations of endocrine precursor cells, immature pancreatic hormone-expressing cells and mature pancreatic hormone-expressing cells. Also disclosed herein are methods of producing such cell cultures and cell populations.

Methods of making oligonucleotide probes
U.S. Patent 10,370,702 (August 6, 2019)

Chao-ting Wu and Brian Beliveau

Abstract: The present invention relates to methods of making linear nucleic acid probes using rolling circle amplification methods.

Compartmentalised screening by microfluidic control
U.S. Patent 10,371,699 (August 6, 2019)

Andrew David Griffiths, David A. Weitz, Darren Roy Link, Keunho Ahn, and Jerome Bibette

Abstract: The invention describes a method for the identification of compounds which bind to a target component of a biochemical system or modulate the activity of the target, comprising the steps of: a) compartmentalizing the compounds into microcapsules together with the target, such that only a subset of the repertoire is represented in multiple copies in any one microcapsule; and b) identifying the compound which binds to or modulates the activity of the target; wherein at least one step is performed under microfluidic control. The invention enables the screening of large repertoires of molecules which can serve as leads for drug development.

Silicon-based visible and near-infrared optoelectric devices
U.S. Patent 10,374,109 (August 6, 2019)

Eric Mazur and James Edward Carey

Abstract: In one aspect, the present invention provides a silicon photodetector having a surface layer that is doped with sulfur inclusions with an average concentration in a range of about 0.5 atom percent to about 1.5 atom percent. The surface layer forms a diode junction with an underlying portion of the substrate. A plurality of electrical contacts allow application of a reverse bias voltage to the junction in order to facilitate generation of an electrical signal, e.g., a photocurrent, in response to irradiation of the surface layer. The photodetector exhibits a responsivity greater than about 1 A/W for incident wavelengths in a range of about 250 nm to about 1050 nm, and a responsivity greater than about 0.1 A/W for longer wavelengths, e.g., up to about 3.5 microns.

Multiplexed genome editing
U.S. Patent 10,375,938 (August 13, 2019)

George M. Church, Luhan Yang, and Marc Guell

Abstract: A method of modulating some or all copies of a gene in a cell is provided including introducing into a cell one or more ribonucleic acid (RNA) sequences that comprise a portion that is complementary to all or a portion of each of the one or more target nucleic acid sequences, and a nucleic acid sequence that encodes a Cas protein and maintaining the cells under conditions in which the Cas protein is expressed and the Cas protein binds and modulates the one or more target nucleic acid sequences in the cell.

Pop-up laminate structures with integrated electronics
U.S. Patent 10,376,326 (August 13, 2019)

Joshua B. Gafford, Samuel B. Kesner, Conor J. Walsh, Michael Karpelson, Robert J. Wood, Zivthan Dubrovsky, Benjamin I. Goldberg, Kathleen O'Donnell, and Michael J. Smith

Abstract: A multi-layer, super-planar laminate structure can be formed from distinctly patterned layers. The layers in the structure can include at least one rigid layer and at least one flexible layer; the rigid layer includes a plurality of rigid segments, and the flexible layer can extend between the rigid segments to serve as a joint. The layers are then stacked and bonded at selected locations to form a laminate structure with inter-layer bonds, and the laminate structure is flexed at the flexible layer between rigid segments to produce an expanded three-dimensional structure, wherein the layers are joined at the selected bonding locations and separated at other locations. A layer with electrical wiring can be included in the structure for delivering electric current to devices on or in the laminate structure.

Synthesis of transcripts using Syn5 RNA polymerase
U.S. Patent 10,378,035 (August 13, 2019)

Bin Zhu, Charles C. Richardson, and Stanley Tabor

Abstract: Methods of in vitro transcription using cyanophage Syn5 RNA polymerase (RNAP) or mutants thereof and transcription conditions are provided.

Leveraging oxidative stress pathways in lactic acid bacteria to promote gut homeostasis
U.S. Patent 10,383,921 (August 20, 2019)

Wendy S. Garrett, Patrick Veiga, Sonia Arora Ballal, Johan van Hylckama Vlieg, Gaelle Quere, and Peggy Garault

Abstract: Disclosed herein are compositions and methods for providing an antioxidant effect to a subject, e.g., modulating or otherwise improving oxidative stress pathways and/or neutralizing or reducing damaging reactive oxygen species (ROS).

Interpenetrating networks with covalent and ionic crosslinks
U.S. Patent 10,383,980 (August 20, 2019)

Jeong-Yun Sun, Xuanhe Zhao, Widusha R. K. Illeperuma, Kyu H. Oh, Joost J. Vlassak, Zhigang Suo, Jianyu Li, and David J. Mooney

Abstract: The invention features a composition comprising a self-healing interpenetrating network hydrogel comprising a first network and a second network. The first network comprises covalent crosslinks and the second network comprises ionic or physical crosslinks. For example, the first network comprises a polyacrylamide polymer and second network comprises an alginate polymer.

Solidifiable composition for preparation of liquid-infused slippery surfaces and methods of applying
U.S. Patent 10,385,181 (August 20, 2019)

Joanna Aizenberg, Michael Aizenberg, Philseok Kim, and Alex Vena

Abstract: A body having a lubricant reservoir is described, comprising: a porous polymeric body; and a lubricating liquid, said lubricating liquid occupying the pores to provide a lubricated porous surface having a lubricant reservoir and a lubricant overlayer over the polymer surface. Also described herein is a system for use in the formation of a low-adhesion and low-friction surface includes a flowable precursor composition comprising a prepolymer and a curing agent, said composition capable of application as a coating over a large surface area; a lubricating liquid that is capable of forming a coating with the hardened precursor composition, wherein the lubricating liquid and hardened polymer together form a coating of lubricating liquid stabilized on and in the hardened polymer; and instructions for applying the precursor composition onto a surface for the purpose of obtaining a low-adhesion and low-friction surface.

De novo design of allosteric proteins
U.S. Patent 10,385,333 (August 20, 2019)

Srivatsan Raman, Noah D. Taylor, and George M. Church

Abstract: Methods and compositions for making and isolating allosteric DNA binding proteins that bind to one or more allosteric effectors to induce a conformation change in the proteins are provided.

Entangled mate sequencing
U.S. Patent 10,385,391 (August 20, 2019)

Frederick P. Roth, Joseph C. Mellor, Yong Lu, and Mark Chee

Abstract: Methods and compositions are provided for performing a set of N DNA sequencing reaction cycles whereby sequence information is obtained for approximately 2*N nucleotide bases.

Soft actuators and soft actuating devices
U.S. Patent 10,385,886 (August 20, 2019)

Dian Yang and George M. Whitesides

Abstract: A soft buckling linear actuator is described, including: a plurality of substantially parallel bucklable, elastic structural components each having its longest dimension along a first axis; and a plurality of secondary structural components each disposed between and bridging two adjacent bucklable, elastic structural components; wherein every two adjacent bucklable, elastic structural components and the secondary structural components in-between define a layer comprising a plurality of cells each capable of being connected with a fluid inflation or deflation source; the secondary structural components from two adjacent layers are not aligned along a second axis perpendicular to the first axis; and the secondary structural components are configured not to buckle, the bucklable, elastic structural components are configured to buckle along the second axis to generate a linear force, upon the inflation or deflation of the cells. Methods of actuation using the same are also described.

Cluster analysis of participant responses for test generation or teaching
U.S. Patent 10,388,177 (August 20, 2019)

Gary King, Brian Lukoff, and Eric Mazur

Abstract: Textual responses to open-ended (i.e., free-response) items provided by participants (e.g., by means of mobile wireless devices) are automatically classified, enabling an instructor to assess the responses in a convenient, organized fashion and adjust instruction accordingly.

Prefabricated alginate-drug bandages
U.S. Patent 10,391,196 (August 27, 2019)

Cathal J. Kearney, Uyanga Tsedev, David J. Mooney, Aristidis Veves, Thomas Michael Braschler, and Sidi A. Bencherif

Abstract: The invention provides a solution to the drawbacks associated with conventional alginate dressings. This invention features improved alginate dressings or bandages as well as a fabrication process that results in an alginate sheet that is preloaded with drug, can be stored in a freeze-dried state, and is compliant and ready to use at the time of administration.

Palladium-mediated ketolization
U.S. Patent 10,392,400 (August 27, 2019)

Jung Hwa Lee, Yoshito Kishi, Ayumi Osawa, and Zhanjie Li

Abstract: Provided herein are palladium-mediated coupling reactions useful in the preparation of ketone-containing organic molecules. The provided methods can be used for the preparation of natural products and pharmaceutical agents, including Eribulin, halichondrins, and analogs thereof. The present invention also provides novel halichondrin analogs which can be prepared via the palladium-mediated coupling reactions. The novel halichondrin analogs can be used in the prevention and/or treatment of diseases or conditions (e.g., proliferative diseases such as cancer).

Blue-light-activated ion channel polypeptides and uses thereof
U.S. Patent 10,392,426 (August 27, 2019)

Nathan Klapoetke, Edward Boyden, Yongku Cho, Brian Y. Chow, Gane K. S. Wong, Adam E. Cohen, and Daniel R. Hochbaum

Abstract: The invention, in some aspects relates to light-activated ion channel polypeptides and encoding nucleic acids and also relates in part to compositions comprising light-activated ion channel polypeptides and methods using light-activated ion channel polypeptides to alter cell activity and function.

Evolution of site-specific recombinases
U.S. Patent 10,392,674 (August 27, 2019)

David R. Liu, David B. Thompson, and Jeffrey L. Bessen

Abstract: Some aspects of the present disclosure provide methods for evolving recombinases to recognize target sequences that differ from the canonical recognition sequences. Some aspects of this disclosure provide evolved recombinases, e.g., recombinases that bind and recombine naturally-occurring target sequences, such as, e.g., target sequences within the human Rosa26 locus. Methods for using such recombinases for genetically engineering nucleic acid molecules in vitro and in vivo are also provided. Some aspects of this disclosure also provide libraries and screening methods for assessing the target site preferences of recombinases, as well as methods for selecting recombinases that bind and recombine a non-canonical target sequence with high specificity.

High-throughput immune sequencing
U.S. Patent 10,392,726 (August 27, 2019)

George M. Church, Francois Vigneault, Uri Laserson, and Ido Bachelet

Abstract: Methods and compositions for determining and/or monitoring the immune state of an individual are provided.

Electrically conductive nanowire Litz braids
U.S. Patent 10,395,791 (August 27, 2019)

Roy Gerald Gordon and Amy Elizabeth Duwel

Abstract: A structure includes a high-strength nanowire core with a first electrically-conductive metal layer bonded to an outer surface thereof. An insulating layer is bonded to an outer surface of the first electrically-conductive metal layer, and a second electrically-conductive metal layer is bonded to an outer surface of the insulating layer. The nanowires are braided into a litz bundle, which reduces electrical losses during transmission of high-frequency current.