Multiplex RNA targeting

Cheng LabCRISPR/Cas + TALENPatentsRNA Splicing + RBPsSynthetic Biology + Genome Engineering
Albert Cheng, Zukai LIU
WO2022187524A1
Publication year: 2023

Provided herein, in some aspects, is a multiplex RNA targeting system that enables live cell imaging and/or modification of multiple RNA targets. Specifically, the disclosure provides a method of live cell imaging of ribonucleic acid (RNA), or targeting RNA in a live cell, comprising: (a) delivering to a cell an RNA-editing complex that comprises a catalytically inactive Cas13 (dCas13) nuclease, a Cas 13 guide RNA (gRNA) comprising an RNA aptamer sequence, and a detectable molecule linked to an RNA-binding domain (RBD), or an RNA effector molecule linked to an RBD sequence that specifically binds to the RNA aptamer sequence; and (b) imaging the detectable molecule or RNA aptamer and RBD binding.

Targeted sequence insertion compositions and methods

Cheng LabCRISPR/Cas + TALENPatentsSynthetic Biology + Genome Engineering
Albert Cheng, Nathaniel Jillette
WO2022032085
Publication year: 2022

Live cell imaging of non-repetitive genomic loci

Cheng LabCRISPR/Cas + TALENImagingPatents
Albert Cheng, Patricia Clow
WO2021034585A1
Publication year: 2021

Activation of lytic genes in cancer cells

Cancer + MetastasisCheng LabCRISPR/Cas + TALENPatents
Albert Cheng, Kwok Wai Lo, Pol Man Tom Hau, Man Wu
WO2021173977A1
Publication year: 2021

Methods and Compositions for Recruiting DNA Repair Proteins

Cheng LabCRISPR/Cas + TALENPatentsSynthetic Biology + Genome Engineering
Albert Cheng,Nathaniel Jillette
WO2020041172
Publication year: 2020

The DNA repair complexes provided herein are, inter alia, useful for editing genome sequences by introducing precise changes in a target site in the presence of a donor sequence. The RNA-guided DNA endonuclease provided herein including embodiments thereof (e.g., Cas9 nuclease or Cas9 nickase) is capable of introducing a strand break (double- or single-strand break) at a target site in the genome of a cell (e.g., gene or transcriptional regulatory sequence) and the break is then predominantly repaired through the mechanism of HDR. By increasing the HDR efficiency significantly and in certain instances decreasing NHEJ at a target site, the compositions and methods provided herein meet the long-felt need of site directed, highly accurate genome editing.

Artificial RNA-guided splicing factors

Cheng LabCRISPR/Cas + TALENDiseasesPatentsRNA Splicing + RBPsSynthetic Biology + Genome Engineering
Albert Cheng, Nathaniel Jillette
WO2020069331
Publication year: 2020

Provided herein, in some aspects, are compositions and methods for artificially modulating alternative splicing, for example, inducing exon inclusion and/or exon exclusion events. In some embodiments, a catalytically inactive programmable nuclease, such as dCasRx, is fused to an RNA-binding protein (or fragment or isoform thereof) and, when guided to a target of interest by a specific guide RNA (gRNA), can regulate alternative splicing in eukaryotic cells.

Transgenic selection methods and compositions

Cheng LabCRISPR/Cas + TALENPatentsSynthetic Biology + Genome Engineering
Albert Cheng,Nathaniel JILLETTE,Menghan DU
WO2019075200A1
Publication year: 2019

The present disclosure provides a split intein selectable marker system for the production and selection of transgenic cells.

Sequence detection systems

Cheng LabCRISPR/Cas + TALENPatentsSynthetic Biology + Genome Engineering
Albert Cheng,Aziz TAGHBALOUT,Nathaniel Lee JILLETTE
WO2019090287A2
Publication year: 2019

The present disclosure, in some embodiments, provides sequence detection systems (sequence detectors) for the detection of specific nucleotides sequences present in the genome of live cells (e.g., single live cells) to achieve, for example, in vivo and in situ imaging, cell selection, and/or cell ablation.

Targeted Enhanced DNA Demethylation

Cheng LabCRISPR/Cas + TALENEpigeneticsPatentsSynthetic Biology + Genome Engineering
Albert Cheng,Aziz TAGHBALOUT,Nathaniel JILLETTE
WO2018053037A1
Publication year: 2018

Provided herein are, inter alia, compositions and methods for the delivery of enhanced demethylation activity to target DNA sequences in a mammalian cell. The compositions and methods are, useful for activity modulation of a targeted gene, or to create a gene regulatory network.

Targeted DNA demethylation and methylation

Cheng LabCRISPR/Cas + TALENEpigeneticsPatentsSynthetic Biology + Genome Engineering
Albert Cheng,Aziz TAGHBALOUT,Nathaniel JILLETTE
WO2018053035A1
Publication year: 2018

Provided herein are, inter alia, compositions and methods for demethylating and methylating a target DNA sequences in a mammalian cell. The compositions and methods are, useful for activity modulation of a targeted gene, or to create a gene regulatory network.

A three-component CRISPR/Cas complex system and uses thereof

Cheng LabCRISPR/Cas + TALENEpigeneticsPatentsSynthetic Biology + Genome Engineering
Haoyi Wang, Albert Cheng, Nathaniel Jillette
WO2016148994
Publication year: 2016

The invention described herein provides compositions and reagents for assembling a tripartite complex at a specific location of a target DNA. The invention also provides methods for using the complex to, for example, label a specific genomic locus, to regulate the expression of a target gene, or to create a gene regulatory network.

Methods of mutating, modifying or modulating nucleic acid in a cell or nonhuman mammal

CRISPR/Cas + TALENPatentsSynthetic Biology + Genome Engineering
Rudolf Jaenisch, Haoyi WANG, Hui Yang, Chikdu SHIVALILA, Wu Albert CHENG
WO2014172470
Publication year: 2014

The invention is directed to a method of mutating one or more target nucleic acid sequences in a stem cell or a zygote comprising introducing into the stem cell or zygote (i) ribonucleic acid (RNA) sequences that comprise a portion that is complementary to a portion of each of the target nucleic acid sequences and comprise a binding site for a CRISPR associated (Cas) protein; and a Cas nucleic acid sequence or a variant thereof that encodes a Cas protein having nuclease activity. The stem cell or zygote is maintained under conditions in which the target nucleic acid sequences are mutated in the stem cell or zygote. The invention is also directed to methods of producing a non human mammal carrying mutations and methods of modulating the expression and/or activity target nucleic acid sequences and cells or zygotes.

Alternatively spliced mRNA isoforms as prognostic indicators for metastatic cancer

Cancer + MetastasisPatentsPhDEraRepresentativeRNA Splicing + RBPs
Christopher Boyce BURGE, Wu Albert CHENG, John S. Condeelis, Frank B. Gertler, Maja H. OKTAY, Irina M. SHAPIRO
WO2012116248 A1
Publication year: 2012

The present invention provides a method for identifying a tumor as likely to metastasize, or likely to have metastasized, comprising obtaining a sample of the tumor and quantitating alternatively spliced mRNA isoforms of a cell motility gene, a cell adhesion gene and /or an actin cytoskeletal remodeling gene in the sample, or any specified genes or the level of RNA binding proteins compared to a predetermined non-metastasizing control.