Harvard faculty Greg Verdine, Junying Yuan, George Church, Dave Weitz, Piotr Sliz, Don Ingber, George Whitesides, Charles Lieber, David Sinclair, Min Dong, Peng Yin, Bruce Bean, David Mooney, Judy Lieberman, Gerhard Wagner, James Butler, and HT Kung are among the inventors issued U.S. patents during March 2017.

The innovations recognized are as follows:

Liver targeted conjugates
U.S. Patent 9,585,964 (March 7, 2017)

Gregory L. Verdine, Yoshihiko Norimine, and Lourdes Gude-Rodriguez

Abstract: Therapeutic conjugates containing a statin or a modified statin (collectively "statin") linked to a therapeutic agent (also referred to as a drug herein) are targeted to the liver by the statin or modified statin and thereby deliver the therapeutic agent to liver cells.

Small molecule inhibitors of necroptosis
U.S. Patent 9,586,880 (March 7, 2017)

Junying Yuan and Emily P. Hsu

Abstract: Compounds having the following structure (VI-A):

or any pharmaceutically acceptable salt or solvate thereof, or any stereoisomer thereof, wherein R_E1, R_E2, R_E3, R_E4, Z_E2 and Z_E3 are as disclosed herein, are provided. Pharmaceutical compositions comprising the compounds, and methods for use of the compounds for treating disorders associated with necrosptosis are also provided.

Orthogonal Cas9 proteins for RNA-guided gene regulation and editing
U.S. Patent 9,587,252 (March 7, 2017)

George M. Church, Kevin Esvelt, and Prashant Mali

Abstract: Methods of modulating expression of a target nucleic acid in a cell are provided including use of multiple orthogonal Cas9 proteins to simultaneously and independently regulate corresponding genes or simultaneously and independently edit corresponding genes.

Manipulation of fluids, fluid components and reactions in microfluidic systems
U.S. Patent 9,588,025 (March 7, 2017)

Seth Fraden, Hakim Boukellal, Yanwei Jia, Seila Selimovic, Amy Rowat, Jeremy Agresti, and David A. Weitz

Abstract: Microfluidic structures and methods for manipulating fluids, fluid components, and reactions are provided. In one aspect, such structures and methods can allow production of droplets of a precise volume, which can be stored/maintained at precise regions of the device. In another aspect, microfluidic structures and methods described herein are designed for containing and positioning components in an arrangement such that the components can be manipulated and then tracked even after manipulation. For example, cells may be constrained in an arrangement in microfluidic structures described herein to facilitate tracking during their growth and/or after they multiply.

Lin28/let-7 crystal structures, purification protocols, and molecular probes suitable for screening assays and therapeutics
U.S. Patent 9,593,141 (March 14, 2017)

Piotr Sliz and Yunsun Nam

Abstract: The invention provides compositions and methods for regulating microRNA (miRNA) biogenesis. The invention also relates to compositions and methods for treating or preventing cancer in a subject in need thereof.

Engineered microbe-targeting molecules and uses thereof
U.S. Patent 9,593,160 (March 14, 2017)

Donald E. Ingber, Michael Super, Jeffrey Charles Way, Mark J. Cartwright, Julia B. Berthet, Dinah R. Super, Martin M. Rottman, and Alexander Watters

Abstract: Described herein are engineered microbe-targeting or microbe-binding molecules, kits comprising the same and uses thereof. Some particular embodiments of the microbe-targeting or microbe-binding molecules comprise a carbohydrate recognition domain of mannose-binding lectin, or a fragment thereof, linked to a portion of a Fc region. In some embodiments, the microbe-targeting molecules or microbe-binding molecules can be conjugated to a substrate, e.g., a magnetic microbead, forming a microbe-targeting substrate (e.g., a microbe-targeting magnetic microbead). Such microbe-targeting molecules and/or substrates and the kits comprising the same can bind and/or capture of a microbe and/or microbial matter thereof, and can thus be used in various applications, e.g., diagnosis and/or treatment of an infection caused by microbes such as sepsis in a subject or any environmental surface. Microbe-targeting molecules and/or substrates can be regenerated after use by washing with a low pH buffer or buffer in which calcium is insoluble.

Microfluidic devices for multiplexed electrochemical detection
U.S. Patent 9,594,051 (March 14, 2017)

George M. Whitesides, Xiujun Li, Frederique Deiss, Zhihong Nie, and Xinyu Liu

Abstract: The multiplexed electrochemical microfluidic paper-based analytical device comprises multiple detection zones for the detection of multiple biochemical analytes from one single sample. Cavity valves integrated on the device will deliver the sample to different detection zones. These analytes include, but are not limited to, urea, creatinine, creatine, glucose, lactate, ethanol, uric acid, cholesterol, pyruvate, creatinine, β-hydroxybutyrate, alanine aminotrasferase, aspartate aminotransferase, alkaline phosphatase, and acetylcholinesterase (or its inhibitors). This system will provide a simple and low-cost POC approach to obtain quantitative and multiple biological information from one sample (e.g. one drop of blood).

Nanoscale wires, nanoscale wire FET devices, and nanotube-electronic hybrid devices for sensing and other applications
U.S. Patent 9,595,685 (March 14, 2017)

Charles M. Lieber, Xiaojie Duan, Ruixuan Gao, Ping Xie, and Xiaocheng Jiang

Abstract: The present invention generally relates to nanotechnology, including field effect transistors and other devices used as sensors (for example, for electrophysiological studies), nanotube structures, and applications. Certain aspects of the present invention are generally directed to transistors such as field effect transistors, and other similar devices. In one set of embodiments, a field effect transistor is used where a nanoscale wire, for example, a silicon nanowire, acts as a transistor channel connecting a source electrode to a drain electrode. In some cases, a portion of the transistor channel is exposed to an environment that is to be determined, for example, the interior or cytosol of a cell. A nanotube or other suitable fluidic channel may be extended from the transistor channel into a suitable environment, such as a contained environment within a cell, so that the environment is in electrical communication with the transistor channel via the fluidic channel. In some embodiments, the rest of the transistor channel may be coated, e.g., so that the electrical properties of the transistor channel reflect the electrical behavior of the environment that the fluidic channel is in communication with. Other aspects of the invention are generally directed to methods of making such sensors, methods of using such sensors, kits involving such sensors, or the like.

Compositions for treating obesity and insulin resistance disorders
U.S. Patent 9,597,347 (March 21, 2017)

David A. Sinclair and Maria Alexander-Bridges

Abstract: Provided herein are methods and compositions for modulating the activity or level of a sirtuin, thereby treating or preventing obesity or an insulin resistance disorder, such as diabetes in a subject. Exemplary methods comprise contacting a cell with a sirtuin activating compound or an inhibitory compound to thereby increase or decrease fat accumulation, respectively.

Engineered botulinum neurotoxin
U.S. Patent 9,598,685 (March 21, 2017)

Min Dong, Lisheng Peng, Pal Erik Gustav Stenmark, and Ronnie Per Arne Berntsson

Abstract: Disclosed herein are botulinum neurotoxin (BoNT) polypeptides with a modified receptor binding domain of Clostridial botulinum serotype B (B-H_c), comprising one or more substitution mutations corresponding to substitution mutations in serotype B, strain 1, V1118M; Y1183M; E1191M; E1191I; E1191Q; E1191T; S1199Y; S1199F; S1199L; SI 20 IV; or combinations thereof. Specific combination mutations include E1 191M and S1199L, E1191M and S1199Y, E1191M and S1199F, E1191Q and S1199L, E1191Q and S 1199Y, or E 1191 Q and S 1199F. Other substitution mutations are also disclosed. Isolated modified receptor binding domains, chimeric molecules, pharmaceutical compositions, and methods of using the same are also disclosed.

Method for forming nanoparticles having predetermined shapes
U.S. Patent 9,598,690 (March 21, 2017)

Wei Sun and Peng Yin

Abstract: Articles and methods for forming nanostructures having unique and/or predetermined shapes are provided. The methods and articles may involve the use of nucleic acid containers as structural molds. For instance, a pre-designed nucleic acid container including a cavity may be used to control the shape-specific growth of nanoparticles. Growth of the nanoparticles within the cavities may be confined by the specific shape of the nucleic acid container. In some embodiments, the resulting nucleic acid-nanoparticle structures can be used to control the orientation and numbers of surface ligands on the surface of nanoparticles. The addressability of the surface ligands can be used to form higher ordered assemblies of the structures.

Light absorption and filtering properties of vertically oriented semiconductor nano wires
U.S. Patent 9,601,529 (March 21, 2017)

Kwanyong Seo, Munib Wober, Paul Steinvurzel, Ethan Schonbrun, Yaping Dan, and Kenneth Crozier

Abstract: A nanowire array is described herein. The nanowire array comprises a substrate and a plurality of nanowires extending essentially vertically from the substrate; wherein: each of the nanowires has uniform chemical along its entire length; a refractive index of the nanowires is at least two times of a refractive index of a cladding of the nanowires. This nanowire array is useful as a photodetector, a submicron color filter, a static color display or a dynamic color display.

Methods, compositions, and kits for treating pain and pruritis
U.S. Patent 9,603,817 (March 28, 2017)

Bruce P. Bean and Clifford J. Woolf

Abstract: The invention features a method for inhibiting one or more voltage-gated ion channels in a cell by contacting the cell with (i) a first compound that activates a channel-forming receptor that is present on nociceptors and/or pruriceptors; and (ii) a second compound that inhibits one or more voltage-gated ion channels when applied to the internal face of the channels but does not substantially inhibit said channels when applied to the external face of the channels, wherein the second compound is capable of entering nociceptors or pruriceptors through the channel-forming receptor when the receptor is activated. The invention also features a quarternary amine derivative or other permanently or transiently charged derivative of a compound that inhibits one or more voltage-gated ion channels when applied to the internal face of the channels but does not substantially inhibit said channels when applied to the external face of the channels.

Materials presenting notch signaling molecules to control cell behavior
U.S. Patent 9,603,894 (March 28, 2017)

Lan Cao, Kamal H. Bouhadir, and David J. Mooney

Abstract: The invention provides a solution to the problem of delivering molecules in a physiologically relevant manner to direct cell fate. For example, a Notch ligand molecule is presented in a microenvironment that mimics the environment encountered in vivo. Accordingly, the invention features a cell delivery vehicle comprising a biocompatible hydrogel or polymer and a composition that binds to a Notch receptor and methods of directing cell fate, e.g., stem cell differentiation, using such compositions.

NMR-based metabolite screening platform
U.S. Patent 9,606,106 (March 28, 2017)

Elizabeth M. O'Day, Judy Lieberman, and Gerhard Wagner

Abstract: Methods that enable one to specifically measure the metabolic product of a particular molecule in relatively few cells, e.g. primary cells, are described. The methods involve optionally preloading cells with labeled substrate (e.g. labeled by ¹³C, ¹⁵N, or ³¹P). The methods allow for easy identification of metabolites that are differentially generated in cells of different phenotypes. The new methods for unbiased multi-dimensional NMR screening and rapid and efficient analysis of the NMR screening identify differentially expressed metabolites in different cell or tissue types. Analysis of the differentially expressed metabolites can present unique druggable targets to which small molecule therapeutics can be designed.

Deformable platforms for biological assays
U.S. Patent 9,606,108 (March 28, 2017)

Ramaswamy Krishnan, Allen Ehrlicher, James Butler, David A. Weitz, Jeffrey J. Fredberg, and Chan Young Park

Abstract: A platform for biological assays includes a base substrate providing structural support to the platform, at least one surface of the base substrate coated with position markers, a first deformable layer positioned on top of the base substrate, and a second deformable layer positioned on top of the first deformable layer, the second deformable layer embedded with deformation markers.

System and method for detecting integrated circuit anomalies
U.S. Patent 9,606,167 (March 28, 2017)

Hsiang-Tsung Kung and Dario Vlah

Abstract: Circuitry, systems and methods for testing integrated circuits for the presence of anomalies. Techniques include applying a plurality of inputs to an integrated circuit under test to obtain a first plurality of measurements at least partially characterizing power leakage in the integrated circuit under test, encode the first plurality of measurements, by computing a plurality of random linear combinations of measurements in the first plurality of measurements, to obtain a second plurality of encoded measurements determining whether the integrated circuit under test contains at least one anomaly based, at least in part, on the second plurality of encoded measurements.