Abstract: Provided herein are methods and compositions for increasing fetal hemoglobin levels in a cell by disrupting BCL11A expression at the genomic level. Also provided herein are methods and compositions relating to the treatment of hemoglobinopathies by reinduction of fetal hemoglobin levels.

Abstract: The present invention is related to the field of gene editing. In particular, the present invention is related to the mutation and/or deletion of genetic abnormalities that result in genetic diseases. For example, an improved CRISPR-Cas fusion protein is disclosed where the Cas protein is a Cas12a protein. The Cas12a protein is fused to a variety of nuclear localization signal (NLS) sequences (e.g., c-myc NLS) that are demonstrated to have unexpected and superior gene editing activity when compared to conventional NLS sequences (e.g., SV40 NLS).

Abstract: The present applications discloses an NLS-optimized SpCas9-based prime editor that improves genome editing efficiency exemplified by endogenous loci in cultured cell lines. Using this genome modification system, tumor formation can be initiated through somatic cell editing in the adult mouse. Furthermore, a dual adeno-associated vims (AAVs) is utilized for the delivery of a split-intein prime editor for correction of in vivo pathogenic mutations.

Abstract: RNA-guided programmable cytosine and adenine base editors are a powerful class of genome editing tool for the introduction of localized base transitions without generating a double-stranded DNA break. Base editors (BE) have an optimal window of activity relative to the PAM recognized by the Cas9 enzyme and these constructs are strand selective. Here we demonstrate that fusion of a programmable DNA-binding domain (pDBD) or another Cas9 orthologue to spCas9-BE, we can produce an RNA-programmable Cas9-BE-pDBD chimera or Cas9-BE-Cas9 chimeras with dramatically improved activities and increased targeting range. Cas9-pDBD or Cas9-Cas9 fusion base editors display an expanded targeting repertoire and achieve highly specific genome editing, which can be tailored to achieve extremely precise genome editing at nearly any genomic locus.

Abstract: The present invention is related to the field of gene editing. In particular, the gene editing is directed toward single nucleotide base editing. For example, such single nucleotide base editing results in a conversion of a OG base pair to a T*A base pair. The high accuracy and precision of the presently disclosed single nucleotide base gene editor is accomplished by an NmeCas9 nuclease that is fused to a nucleotide deaminase protein. The compact nature of the NmeCas9 coupled with a larger number of compatible protospacer adjacent motifs provide the Cas9 fusion constructs contemplated herein to have a gene editing window that can edit sites that are not targetable by other conventional SpyCas9 base editor platforms.

Abstract: A binocular image-based model training method and apparatus, and a data processing device are provided. An image matching model includes a teacher model and a student model. In the method, two groups of sample images acquired at different time points by a binocular image acquisition apparatus are first obtained; then, for any two sample images in the two groups of sample images, optical flow estimation is performed according to a preset geometric constraint between the two sample images by means of the teacher model, so as to obtain a more accurate high-confidence optical flow estimation result, the preset geometric constraint being a binocular image-based geometric constraint; and finally, machine learning training of image element matching is performed on the student model by using the two sample image, with the high-confidence optical flow estimation result taken as labeling information.

Abstract: Provided are a monocular image-based model training method and apparatus, and a data processing device. The method includes: first obtaining a first training image and a second training image acquired at different time points by a monocular image acquisition apparatus; then obtaining a first optical flow prediction result from the first training image to the second training image according to a photometric loss between the first training image and the second training image; and taking the first optical flow prediction result as an agent label, and performing optical flow prediction training by using the first training image and the second training image.

Abstract: Provided herein are synthetic nucleic acids that encode a CRISPR enzyme fused to a series of nuclear localization signal sequences for the use of altering expression of a gene in a cell. Further provided herein are methods for altering gene expression in a cell comprising introducing the synthetic nucleic acids and a guide RNA, or a polypeptide and a guide RNA into a cell. In certain embodiments the cell is a quiescent cell, for example, a hematopoietic stem cell.

Abstract: Provided herein are methods and compositions for increasing fetal hemoglobin levels in a cell by disrupting BCL11A expression at the genomic level. Also provided herein are methods and compositions relating to the treatment of hemoglobinopathies by reinduction of fetal hemoglobin levels.

Abstract: The present disclosure discloses a voice remote controller and a power supplying method thereof. The voice remote controller comprises: a noise gathering module for gathering ambient noise at the periphery of the voice remote controller by using a sound aperture array; a sound-electricity converting module for converting the ambient noise gathered by the noise gathering module into an electrical signal; and an energy storing module for storing the electrical signal converted by the sound-electricity converting module as electric energy and supplying power to the voice remote controller. According to the present disclosure, ambient noise is gathered by a sound aperture array and converted into electricity used as the working energy, thereby avoiding battery replacing or frequent charging. When a voice function of a voice remote controller is turned off, all of the gathered ambient noise is converted into electricity, thereby improving the energy utilization rate.

Abstract: The present disclosure discloses a voice remote controller and a power supplying method thereof. The voice remote controller comprises: a noise gathering module for gathering ambient noise at the periphery of the voice remote controller by using a sound aperture array; a sound-electricity converting module for converting the ambient noise gathered by the noise gathering module into an electrical signal; and an energy storing module for storing the electrical signal converted by the sound-electricity converting module as electric energy and supplying power to the voice remote controller. According to the present disclosure, ambient noise is gathered by a sound aperture array and converted into electricity used as the working energy, thereby avoiding battery replacing or frequent charging. When a voice function of a voice remote controller is turned off, all of the gathered ambient noise is converted into electricity, thereby improving the energy utilization rate.