Harvard faculty Timothy Mitchison, Venkatesh Narayanamurti, Kevin Eggan, Adam Cohen, Amir Yacoby, Hongkun Park, Marko Loncar, Mikhail Lukin, Christoph Lange, Gary King, Ulrich von Andrian, David Liu, and Gregory Verdine are among the inventors issued U.S. patents during December 2016.

The innovations recognized are as follows:

Methods and compositions for labeling nucleic acids
U.S. Patent 9,512,465 (December 6, 2016)

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.

Phase transition devices and smart capacitive devices
U.S. Patent 9,515,256 (December 6, 2016)

Shriram Ramanathan, Dmitry Ruzmetov, Venkatesh Narayanamurti, and Changhyun Ko

Abstract: Phase transition devices may include a functional layer made of functional material that can undergo a change in conductance in response to an external stimulus such as an electric or magnetic or optical field, or heat. The functional material transitions between a conducting state and a non-conducting state, upon application of the external stimulus. A capacitive device may include a functional layer between a top electrode and a bottom electrode, and a dielectric layer between the functional layer and the top electrode. A three terminal phase transition switch may include a functional layer, for example a conductive oxide channel, deposited between a source and a drain, and a gate dielectric layer and a gate electrode deposited on the functional layer. An array of phase transition switches and/or capacitive devices may be formed on a substrate, which may be made of inexpensive flexible material.

Methods to treat neurodegenerative diseases
U.S. Patent 9,517,223 (December 13, 2016)

Clifford J. Woolf, Brian Wainger, Evangelos Kiskinis, and Kevin Eggan

Abstract: The present invention is based on the discovery that motor neurons derived from patients with a neurodegenerative disease have decreased delayed rectifier potassium current and increased persistent sodium current compared to motor neurons derived from control healthy individuals. The present invention is also based on the discovery that the class of compounds known as "potassium channel openers" can be used to treat neurodegenerative diseases, including ALS, Parkinson's disease, Alzheimer's disease, epilepsy, and pain.

Optogenetic probes for measuring membrane potential
U.S. Patent 9,518,103 (December 13, 2016)

Adam E. Cohen, Daniel Hochbaum, Peng Zou, Samouil Leon Farhi, Robert Earl Campbell, Yongxin Zhao, and Daniel Jed Harrison

Abstract: Provided herein are variants of an archaerhodopsin useful for application such as optical measurement of membrane potential. The present invention also relates to polynucleotides encoding the variants; nucleic acid constructs, vectors, cells comprising the polynucleotides, and cells comprising the polypeptides; and methods of using the variants.

Synthetic diamond materials for quantum and optical applications and methods of making the same
U.S. Patent 9,518,336 (December 13, 2016)

Matthew Markham, Alastair Stacey, Nathalie De Leon, Yiwen Chu, Brendan John Shields, Birgit Judith Maria Hausmann, Patrick Maletinsky, Ruffin Eley Evans, Amir Yacoby, Hongkun Park, Marko Loncar, and Mikhail D. Lukin

Abstract: A synthetic diamond material comprising one or more spin defects having a full width half maximum intrinsic inhomogeneous zero phonon line width of no more than 100 MHz. The method for obtain such a material involves a multi-stage annealing process.

Systems and methods for genetic data compression
U.S. Patent 9,519,650 (December 13, 2016)

Christoph Lange and Dandi Qiao

Abstract: Genetic data may be compressed efficiently by selecting for each bi-allelic marker, from among multiple compression algorithms with different associated storage requirements that depend on the minor allele frequency of the respective marker, the algorithm that has the lowest storage requirements. Efficient approaches compress, store, and load pedigree file data. A hybrid method is used that selects between multiple alternative compression algorithms whose performance depends on the frequency of certain observable genetic variations. The hybrid method may achieve higher compression ratios than PLINK or PBAT. Further, it results in a compressed data format that, generally, does not require any overhead memory space and CPU time for decompression, and, consequently, has shorter loading times for compressed files than the binary format in PLINK or PBAT. Moreover, the compressed data fonnat supports parallel loading of genetic information, which decreases the loading time by a factor of the number of parallel jobs.

Method and apparatus for selecting clusterings to classify a data set
U.S. Patent 9,519,705 (December 13, 2016)

Gary King and Justin Grimmer

Abstract: In a computer assisted clustering method, a clustering space is generated from fixed basis partitions that embed the entire space of all possible clusterings. A lower dimensional clustering space is created from the space of all possible clusterings by isometrically embedding the space of all possible clusterings in a lower dimensional Euclidean space. This lower dimensional space is then sampled based on the number of documents in the corpus. Partitions are then developed based on the samples that tessellate the space. Finally, using clusterings representative of these tessellations, a two-dimensional representation for users to explore is created.

Vaccine nanotechnology
U.S. Patent 9,526,702 (December 27, 2016)

Ulrich H. von Andrian, Omid C. Farokhzad, Robert S. Langer, Tobias Junt, Elliott Ashley Moseman, Liangfang Zhang, Pamela Basto, Matteo Iannacone, and Frank Alexis

Abstract: The present invention provides compositions and systems for delivery of nanocarriers to cells of the immune system. The invention provides vaccine nanocarriers capable of stimulating an immune response in T cells and/or B cells, in some embodiments, comprising at least one immunomodulatory agent, and optionally comprising at last one targeting moiety and optionally at least one immunostimulatory agent. The invention provides pharmaceutical compositions comprising inventive vaccine nanocarriers. The present invention provides methods of designing, manufacturing, and using inventive vaccine nanocarriers and pharmaceutical compositions thereof. The invention provides methods of prophylaxis and/or treatment of diseases, disorders, and conditions comprising administering at least one inventive vaccine nanocarrier to a subject in need thereof.

Delivery system for functional nucleases
U.S. Patent 9,526,784 (December 27, 2016)

David R. Liu, John Anthony Zuris, and David B. Thompson

Abstract: Compositions, methods, strategies, kits, and systems for the supercharged protein-mediated delivery of functional effector proteins into cells in vivo, ex vivo, or in vitro are provided. Compositions, methods, strategies, kits, and systems for delivery of functional effector proteins using cationic lipids and cationic polymers are also provided. Functional effector proteins include, without limitation, transcriptional modulators (e.g., repressors or activators), recombinases, nucleases (e.g., RNA-programmable nucleases, such as Cas9 proteins; TALE nuclease, and zinc finger nucleases), deaminases, and other gene modifying/editing enzymes. Functional effector proteins include TALE effector proteins, e.g., TALE transcriptional activators and repressors, as well as TALE nucleases. Compositions, methods, strategies, and systems for the delivery of functional effector proteins into cells is useful for therapeutic and research purposes, including, but not limited to, the targeted manipulation of a gene associated with disease, the modulation of the expression level of a gene associated with disease, and the programming of cell fate.

Stabilized p53 peptides and uses thereof
U.S. Patent 9,527,896 (December 27, 2016)

Federico Bernal, Loren D. Walensky, Gregory L. Verdine, and Stanley J. Korsmeyer

Abstract: Cross-linked peptides related to human p53 and bind to HMD2 or a family member of HDM2 useful for promoting apoptosis, e.g., in the treatment of and identifying therapeutic agents that binding to HMD2 or a family member of HDM2.