Abstract: Disclosed herein are polynucleotides encoding multi-epitope polypeptides and assemblies thereof, and their use for treating or limiting Toxoplasma gondii infection.

Abstract: Provided herein are engineered HSV-1 vectors comprising a modified HSV-1 genome. The engineered HSV-1 vectors can be used to deliver genetic circuits (e.g., up to 100 kb) to cells in vitro or in vivo. Methods of treating or diagnosing a disease (e.g., cancer) using the engineered HSV-1 vectors described herein are also provided.

Abstract: Provided herein, in some aspects, are antibody expression systems comprising DNA launched RNA replicons for high level antibody expression. In some embodiments, the antibody is a therapeutic antibody. In some embodiments, the antibody is an immune check point inhibitor. Methods of using the antibody expression system for treating diseases (e.g., cancer) are also provided.

Abstract: The present disclosure relates to synthetic oncolytic viruses comprising a lipid nanoparticle comprising one or more types of lipid and a self-amplifying replicon RNA comprising a sequence that encodes an immunomodulatory molecule.

Abstract: The disclosure provides novel large serine recombinases and their respective recognition sites, as well as libraries of orthogonal recombinase recognition sites. Uses of the large serine recombinases, recognition sites, and libraries of orthogonal recombinase recognition sites also are provided.

Abstract: Compositions and methods are described for inducing an immune response against an immunogen in humans. The induced immune response is obtained by administering a heterologous prime-boost combination of an in vitro transcribed (IVT) self-replicating RNA (repRNA) and an adenovirus vector. The compositions and methods can be used to provide a protective immunity against a disease, such as a viral infection or a cancer, in humans.

Abstract: The disclosure provides methods for an in vitro evolution technique to identify and characterize mutations in the non-structural genes of an alphavirus replicon that increase the strength and persistence of expression of the replicon genome. Also provided herein are in vivo methods for administering to an animal model a mutated alphavirus replicon that codes for a gene of experimental or therapeutic interest in the subgenome of the alphavirus replicon. The mutations identified herein improve the therapeutic potential of self-replicating RNA, which may have implications for cancer immunotherapy and beyond, e.g., for vaccination or gene therapy.

Abstract: Disclosed herein are lipid nanoparticles having a specific composition, compositions including such lipid nanoparticles, and methods of treatment using such lipid nanoparticles and compositions.

Abstract: The present invention provides compositions and methods for programming mammalian cells to perform desired functions. In particular, the present invention provides compositions and methods for programming stem cells to differentiate into a desired cell type. A quorum sensing systems that regulates the expression of cell fate regulators is introduced into mammalian host cells, such as stem cells. The quorum sensing systems generally comprises vectors that express the components of a bacterial quorum sensing pathway, including proteins which catalyze the synthesis of an autoinducer and a gene encoding a regulatory partner of the autoinducer, and vectors in which genes encoding cell fate regulators are operably linked to a promoter induced by the autoinducer/regulatory partner complex.

Abstract: Provided herein are genetic circuits and cell state classifiers for detecting the microRNA profile of a cell. The cell state classifiers of the present disclosure utilize phosphorylation state of a transcription factor to control classifier output. Kinases and phosphatase pairs that function in phosphorylating or dephosphorylating the transcription factor are integrated into the circuit, their expression tuned by the presence of microRNAs of interest (e.g., in a cell). The genetic circuits and cell state classifiers may be used in various applications (e.g., therapeutic or diagnostic applications).

Abstract: Provided is a modular construction of synthetic gene circuits in mammalian cells using TALE transcriptional repressors.

Abstract: Provided herein are genetic circuits and cell state classifiers for detecting the microRNA profile of a cell. In some embodiments, the cell state classifiers described herein utilize an endoribonuclease and a self-amplifying RNA molecule for controlling the expression of an output molecule. In some embodiments, the cell state classifiers described herein are encoded on a single RNA transcript, which is then processed to produce individual genetic circuits that function independently. The genetic circuits and cell state classifiers described herein may be used in various applications (e.g., therapeutic or diagnostic applications).

Abstract: Aspects of the present disclosure are directed to methods and compositions for the production of heterogeneous tissue from human induced pluripotent stem (hiPS) cells.

Abstract: Disclosed herein are polynucleotides encoding multi-epitope polypeptides and assemblies thereof, and their use for treating or limiting Toxoplasma gondii infection.

Abstract: Engineered synthetic RNA-based genetic circuits are provided that are regulated exclusively at the post-transcriptional level.

Abstract: Systems and methods facilitating removal of content from audio files are described. A method includes identifying a sound recording in a first audio file, identifying a reference file having at least a defined level of similarity to the sound recording, and processing the first audio file to remove the sound recording and generate a second audio file. In some embodiments, winner-take-all coding and Hough transforms are employed for determining alignment and rate adjustment of the reference file in the first audio file. After alignment, the reference file is filtered in the frequency domain to increase similarity between the reference file and the sound recording. The frequency domain representation (FR) of the filtered version is subtracted from the FR first audio and the result converted to a time representation of the second audio file. In some embodiments, spectral subtraction is also performed to generate a further improved second audio file.

Abstract: Provided herein are genetic circuits and encoded RNA transcripts that produce an output molecule in response to an RNA cleavage event that removes a degradation signal. In some embodiments, the genetic circuits described herein may be used for detecting RNA cleaver activities (e.g., in a cell). Methods of using the genetic circuits described herein in diagnostic or therapeutic applications are also provided.

Abstract: Provided herein are genetic circuits and cell state classifiers for detecting the microRNA profile of a cell. The cell state classifiers of the present disclosure are designed to incorporate multiple genetic circuits integrated together by transcriptional or translational control. Multiple inputs can be sensed simultaneously by coupling their detection to different portions of the genetic circuit such that the output molecule is produced only when the correct input profile of miRNAs is detected. The genetic circuits and cell state classifiers may be used in various applications (e.g., therapeutic or diagnostic applications).

Abstract: Engineered synthetic RNA-based genetic circuits are provided that are regulated exclusively at the post-transcriptional level.

Abstract: Aspects of the invention relate to reconfigurable chassis that allow for rapid construction and optimization of biocircuits.