Harvard faculty George Whitesides, Peng Yin, Joanna Aizenberg, Don Ingber, George Church, Adrian Salic, Timothy Mitchison, Yoshito Kishi, Rob Wood, Daniel Branton, David Mooney, David Scadden, David Weitz, Stuart Orkin, and Vijay Sankaran are among the inventors issued U.S. patents in February 2020.

The innovations recognized are as follows:

Portable prosthetic hand with soft pneumatic fingers
U.S. Patent 10,548,745 (February 4, 2020)

Bobak Mosadegh, Brandon Grant Gerberich, and George M. Whitesides

Abstract: A finger actuator, includes a plurality of fluidically interconnected inflatable chambers, wherein each chamber comprises outer walls having an embedded extensible layer selected to constrain radial expansion and freestanding inner walls; and an inextensible layer connected to the chambers at a base of the chambers, the inextensible layer comprising a flexible polymer and having an embedded inextensible layer that extends along the length of the finger actuator.

Single-stranded DNA nanostructures
U.S. Patent 10,550,145 (February 4, 2020)

Dongran Han, Cameron Myhrvold, and Peng Yin

Abstract: The present disclosure relates to nanostructures assembled from nucleic acid consisting of a single strand of DNA rationally-designed to self-assemble into a hairpin loop, helical domains, and locking domains.

Genetic reprogramming of bacterial biofilms
U.S. Patent 10,550,160 (February 4, 2020)

Neel Satish Joshi, Peter Q. Nguyen, and Zsofia Magarian

Abstract: Described herein are methods and compositions relating to engineered curli fibers, e.g. CsgA polypeptide. In some embodiments, the methods and compositions described herein relate to functionalized biofilms.

Slippery liquid-infused porous surfaces and biological applications thereof
U.S. Patent 10,550,272 (February 4, 2020)

Joanna Aizenberg, Benjamin Hatton, Donald Ingber, Michael Super, and Tak Sing Wong

Abstract: A self-healing, scratch resistant slippery surface that is manufactured by wicking a chemically-inert, high-density liquid coating over a roughened solid surface featuring micro and nanoscale topographies is described. Such a slippery surface shows anti-wetting properties, as well as exhibits significant reduction of adhesion of a broad range of biological materials, including particles in suspension or solution. Specifically, the slippery surfaces can be applied to medical devices and equipment to effectively repel biological materials such as blood, and prevent, reduce, or delay coagulation and surface-mediated clot formation. Moreover, the slippery surfaces can be used to prevent fouling by microorganisms such as bacteria.

Systems, methods and compositions for sequence manipulation with optimized functional CRISPR-Cas systems
U.S. Patent 10,550,372 (February 4, 2020)

Silvana Konermann, Alexandro Trevino, Mark Brigham, Fei Ran, Patrick Hsu, Chie-yu Lin, Osamu Nureki, Hiroshi Nishimasu, Ryuichiro Ishitani, and Feng Zhang

Abstract: The invention provides for systems, methods, and compositions for altering expression of target gene sequences and related gene products. Provided are structural information on the Cas protein of the CRISPR-Cas system, use of this information in generating modified components of the CRISPR complex, vectors and vector systems which encode one or more components or modified components of a CRISPR complex, as well as methods for the design and use of such vectors and components. Also provided are methods of directing CRISPR complex formation in eukaryotic cells and methods for utilizing the CRISPR-Cas system. In particular the present invention comprehends optimized functional CRISPR-Cas enzyme systems.

Methods for selecting microbes from a diverse genetically modified library to detect and optimize the production of metabolites
U.S. Patent 10,550,384 (February 4, 2020)

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

Abstract: The present invention relates to genetically modified bacteria and methods of optimizing genetically modified bacteria for the production of a metabolite.

Methods and compositions for labeling nucleic acids
U.S. Patent 10,550,422 (February 4, 2020)

Kyle R. Gee, Brian Agnew, Adrian Salic, and Timothy J. Mitchison

Abstract: The present invention relates to methods for the labeling of nucleic acid polymers in vitro and in vivo. Certain methods are provided that include a [3+2] cycloaddition between a nucleotide analogue incorporated into a nucleic acid polymer and a reagent attached to a label. Other methods are provided that include a Staudinger ligation between a nucleotide analogue incorporated into a nucleic acid polymer and a reagent comprising a substituted triarylphosphine attached to a label. Such methods do not require fixation and denaturation and therefore can be applied to the labeling of nucleic acid polymers in living cells and in organisms. Also provided are methods for measuring cellular proliferation. In these methods, the amount of label incorporated into the DNA is measured as an indication of cellular proliferation. The methods of the invention can be used in a wide variety of applications including clinical diagnosis of diseases and disorders in which cellular proliferation is involved, toxicity assays, and as a tool for the study of chromosomes' ultrastructures.

Methods and compositions for improving detection and/or capture of a target entity
U.S. Patent 10,551,379 (February 4, 2020)

Michael Super, Mark J. Cartwright, Martin M. Rottman, and Julie A. Tomolonis

Abstract: Methods, compositions, kits and systems for detecting and/or capturing a target entity in a sample are disclosed. In particular, the methods, compositions and kits described herein can be used for pretreatment of target-binding agents with a blocking agent to reduce non-target binding in a complex matrix (e.g., blood). Methods and compositions for detecting and/or capturing a microbe in a test sample, including bodily fluids such as blood and tissues of a subject, food, water, and environmental surfaces are also disclosed.

Acoustophoretic printing apparatus and method
U.S. Patent 10,556,428 (February 11, 2020)

Daniele Foresti, Dimos Poulikakos, and Manish Kumar Tiwari

Abstract: The present invention contains a printing apparatus and a method, e.g., for ejecting inks (i.e., pure liquids, mixtures, colloids, etc.) for a very broad range of physical properties (such as viscosity). Acoustic forces 3a may be generated by an emitter 1 and a reflector 2 to detach droplets 10 from a nozzle 6. The ink may be advanced through the nozzle 6 by a standard back pressure system 5. A reflectorless chamber 7 may enhance acoustic forces 8a and the droplets 10 may be ejected at a bottom 9 of said chamber 7, so that droplets 10 may be deposited on any substrate 11.

Synthesis of halichondrin analogs and uses thereof
U.S. Patent 10,556,910 (February 11, 2020)

Yoshito Kishi, Atsushi Ueda, Akihiko Yamamoto, and Daisuke Kato

Abstract: The present invention provides halichondrin analogs, such as compounds of Formula (I). The compounds may bind to microtubule sites, thereby inhibiting microtubule dynamics. Also provided are methods of synthesis, pharmaceutical compositions, kits, methods of treatment, and uses that involve the compounds for treatment of a proliferative disease (e.g., cancer). Compounds of the present invention are particularly useful for the treatment of metastatic breast cancer, non-small cell lung cancer, prostate cancer, and sarcoma. The included methods of synthesis are useful for the preparation of compounds of Formula (I)-(III) along with naturally occurring halicondrins (e.g., halichondrin B & C, norhalichondrin A, B, & C, and homohalichondrin A, B, & C). Also included are methods for interconverting between the halichondrins, norhalichondrins, and homohalichondrins and their unnatural epimers at the C38 ketal stereocenter through the use of an acid-mediated equilibration.

Pneumatic sensing actuator
U.S. Patent 10,562,260 (February 18, 2020)

Yong-Lae Park, Robert J. Wood, Jobim Jose Robinsantos, and Eugene C. Goldfield

Abstract: A pneumatic artificial muscle (PAM) actuator body can be formed from an elastic material that includes an inflatable chamber and a restraining component, such as flexible, but inextensible fibers, that causes the actuator to contract when the chamber is inflated with fluid (e.g., air or water). The actuator body can be cylindrical or flat. The actuator body can include a sensor layer formed of an elastic material including a microchannel filled with a conductive fluid to sense the expansion of the actuator body. The sensor layer can be configured to expand when the actuator body is inflated causing the electrical resistance of the conductive fluid to change. A sensor layer between the actuator body and restraining component can be used to measure changes in the contraction force of the actuator and a sensor layer outside of the restraining component can be used to measure changes in the length of the actuator.

Genome engineering
U.S. Patent 10,563,225 (February 18, 2020)

George M. Church, Luhan Yang, Marc Guell, and Joyce Lichi Yang

Abstract: Methods are provided for the use of Cas9 in genome engineering of stem cells. Methods include introducing into the stem cell a first foreign nucleic acid encoding a guide RNA complementary to a target DNA and which guides a Cas9 enzyme to the target DNA, wherein the RNA and the enzyme are members of a co-localization complex for the target DNA, introducing into the stem cell a second foreign nucleic acid encoding a donor nucleic acid sequence, wherein the guide RNA and the donor nucleic acid sequences are expressed, wherein the guide RNA and the Cas 9 enzyme co-localize to the target DNA, the Cas 9 enzyme cleaves the target DNA and the donor nucleic acid is inserted into the target DNA to produce altered DNA in the stem cell.

In situ nucleic acid sequencing of expanded biological samples
U.S. Patent 10,563,257 (February 18, 2020)

Edward Stuart Boyden, Fei Chen, Shahar Alon, George Church, Paul Warren Tillberg, Adam Henry Marblestone, and Evan R. Daugharthy

Abstract: The invention provides in situ nucleic acid sequencing to be conducted in biological specimens that have been physically expanded. The invention leverages the techniques for expansion microscopy (ExM) to provide new methods for in situ sequencing of nucleic acids as well as new methods for fluorescent in situ sequencing (FISSEQ) in a new process referred to herein as "expansion sequencing" (ExSEQ).

Nanometric material having a nanopore enabling high-sensitivity molecular detection and analysis
U.S. Patent 10,564,144 (February 18, 2020)

Slaven Garaj, Jene A. Golovchenko, and Daniel Branton

Abstract: There is provided a substantially bare, self-supported single-layer graphene membrane including a nanopore extending through a thickness of the graphene membrane from a first to a second membrane surface opposite the first graphene membrane surface. A connection from the first graphene membrane surface to a first reservoir provides, at the first graphene membrane surface, a species in an ionic solution to the nanopore, and a connection from the second graphene membrane surface to a second reservoir is provided to collect the species and ionic solution after translocation of the species and ionic solution through the nanopore from the first graphene membrane surface to the second graphene membrane surface. An electrical circuit is connected on opposite sides of the nanopore to measure flow of ionic current through the nanopore in the graphene membrane.

Method of eliciting an anti-tumor immune response with controlled delivery of TLR agonists in porous polymerlc devices
U.S. Patent 10,568,949 (February 25, 2020)

Omar Abdel-Rahman Ali, Glenn Dranoff, and David J. Mooney

Abstract: The present invention comprises compositions, methods, and devices for creating an stimulating an antigen-specific dendritic cell immune response. Devices and methods provide prophylactic and therapeutic immunity to subjects against cancer and infectious agents.

Compositions and methods for non-myeloablative conditioning
U.S. Patent 10,570,207 (February 25, 2020)

David T. Scadden, Rahul Palchaudhuri, Derrick J. Rossi, and Agnieszka D. Czechowicz

Abstract: Disclosed herein are non-myeloablative antibody-toxin conjugates and compositions that target cell surface markers, such as the CD34, CD45 or CD117 receptors, and related methods of their use to effectively conditioning a subject's tissues (e.g., bone marrow tissue) prior to engraftment or transplant. The compositions and methods disclosed herein may be used to condition a subject's tissues in advance of, for example, hematopoietic stem cell transplant and advantageously such compositions and methods do not cause the toxicities that are commonly associated with traditional conditioning methods.

Acoustic waves in microfluidics
U.S. Patent 10,570,361 (February 25, 2020)

David A. Weitz, Thomas Franke, Achim Wixforth, Lothar Schmid, Jeremy Agresti, and Adam R. Abate

Abstract: Various aspects of the present invention relate to the control and manipulation of fluidic species, for example, in microfluidic systems. In one set of embodiments, droplets may be sorted using surface acoustic waves. The droplets may contain cells or other species. In some cases, the surface acoustic waves may be created using a surface acoustic wave generator such as an interdigitated transducer, and/or a material such as a piezoelectric substrate. The piezoelectric substrate may be isolated from the microfluidic substrate except at or proximate the location where the droplets are sorted, e.g., into first or second microfluidic channels. At such locations, the microfluidic substrate may be coupled to the piezoelectric substrate (or other material) by one or more coupling regions. In some cases, relatively high sorting rates may be achieved, e.g., at rates of at least about 1,000 Hz, at least about 10,000 Hz, or at least about 100,000 Hz, and in some embodiments, with high cell viability after sorting.

Modulation of BCL11A for treatment of hemoglobinopathies
U.S. Patent 10,570,392 (February 25, 2020)

Stuart H. Orkin and Vijay G. Sankaran

Abstract: The invention relates to methods and uses of modulating fetal hemoglobin expression (HbF) in a hematopoietic progenitor cells via inhibitors of BCL11A expression or activity, such as RNAi and antibodies.

Methods of introducing nucleic acids into cellular DNA
U.S. Patent 10,570,400 (February 25, 2020)

Marc J. Lajoie, Christopher J. Gregg, Joshua A. Mosberg, and George M. Church

Abstract: A method of introducing a nucleic acid sequence into a cell is provided where the cell has impaired or inhibited or disrupted DnaG primase activity or impaired or inhibited or disrupted DnaB helicase activity, or larger or increased gaps or distance between Okazaki fragments or lowered or reduced frequency of Okazaki fragment initiation, or the cell has increased single stranded DNA (ssDNA) on the lagging strand of the replication fork including transforming the cell through recombination with a nucleic acid oligomer.