Paul D. Donohoue
A5020633750- CRISPR and Genetic Engineering
- CAR-T cell therapy research
- RNA and protein synthesis mechanisms
- Advanced biosensing and bioanalysis techniques
- Innovation and Socioeconomic Development
- Biosimilars and Bioanalytical Methods
- T-cell and B-cell Immunology
- RNA regulation and disease
- RNA modifications and cancer
- Viral Infectious Diseases and Gene Expression in Insects
- Advancements in Semiconductor Devices and Circuit Design
- Nitrogen and Sulfur Effects on Brassica
- Pancreatic function and diabetes
- Biofuel production and bioconversion
- Immune Cell Function and Interaction
- Microbial Metabolic Engineering and Bioproduction
- Biochemical effects in animals
- Nanowire Synthesis and Applications
- Tryptophan and brain disorders
- Protein Hydrolysis and Bioactive Peptides
- Cell Adhesion Molecules Research
- Insect symbiosis and bacterial influences
- RNA Research and Splicing
- RNA Interference and Gene Delivery
- Phytase and its Applications
Caribou Biosciences (United States)
2014-2024
University of California, Davis
2008-2009
The target DNA specificity of the CRISPR-associated genome editor nuclease Cas9 is determined by complementarity to a 20-nucleotide segment in its guide RNA. However, can bind and cleave partially complementary off-target sequences, which raises safety concerns for use clinical applications. Here, we report crystallographic structures bound bona fide substrates, revealing that binding enabled range noncanonical base-pairing interactions within guide:off-target heteroduplex. Off-target...
The development of CRISPR genome editing has transformed biomedical research. Most applications reported thus far rely upon the Cas9 protein from Streptococcus pyogenes SF370 (SpyCas9). With many RNA guides, wildtype SpyCas9 can induce significant levels unintended mutations at near-cognate sites, necessitating substantial efforts toward strategies to minimize off-target activity. Although genome-editing potential thousands other orthologs remains largely untapped, it is not known how will...
Allogeneic chimeric antigen receptor (CAR) T cell therapies hold the potential to overcome many of challenges associated with patient-derived (autologous) CAR cells. Key considerations in development allogeneic include prevention graft-vs-host disease (GvHD) and suppression allograft rejection. Here, we describe preclinical data supporting ongoing first-in-human clinical study, CaMMouflage trial (NCT05722418), evaluating CB-011 patients relapsed/refractory multiple myeloma. is a...
The essential enzymatic cofactor NAD+ can be synthesized in many eukaryotes, including Saccharomyces cerevisiae and mammals, using tryptophan as a starting material. Metabolites along the pathway or on branches have important biological functions. For example, kynurenic acid act an NMDA antagonist, thereby functioning neuroprotectant wide range of pathological states. N-Formyl kynurenine formamidase (FKF) catalyzes second step biosynthetic by hydrolyzing N-formyl to produce formate. S. FKF...
Background aimsTherapeutic disruption of immune checkpoints has significantly advanced the armamentarium approaches for treating cancer. The prominent role programmed death-1 (PD-1)/programmed death ligand-1 axis downregulating T cell function offers a tractable strategy enhancing disease-modifying impact CAR-T therapy.MethodsTo address checkpoint interference, primary human cells were genome edited with next-generation CRISPR-based platform (Cas9 chRDNA) by knockout PDCD1 gene encoding PD-1...
ABSTRACT Background The development of CRISPR genome editing has transformed biomedical research. Most applications reported thus far rely upon the Cas9 protein from Streptococcus pyogenes SF370 (SpyCas9). With many RNA guides, wild-type SpyCas9 can induce significant levels unintended mutations at near-cognate sites, necessitating substantial efforts toward strategies to minimize off-target activity. Although genome-editing potential thousands other orthologs remains largely untapped, it is...
ABSTRACT The target DNA specificity of the CRISPR-associated genome editor nuclease Cas9 is determined by complementarity to a 20-nucleotide segment in its guide RNA. However, can bind and cleave partially complementary off-target sequences, which raises safety concerns for use clinical applications. Here we report crystallographic structures bound bona fide substrates, revealing that binding enabled range non-canonical base pairing interactions within guide–off-target heteroduplex....
<p>Antitumor activity of CB-011 CAR-T cells in a xenograft model multiple myeloma.</p>
<p>CB-011 immune-cloaking armoring strategy suppresses cytotoxic T and NK cell–mediated allograft rejection.</p>
<p>In vitro serial rechallenge assay demonstrates long-term cytotoxicity activity of CB-011 against BCMA+ tumor cells.</p>
<p>Gamma-secretase inhibitor RO4929097 increases BCMA expression on-target cell lines but does not improve CB-011 antitumor efficacy.</p>
<p>CB-011 cells exhibit in vitro antitumor activity against PBMCs from patients with multiple myeloma.</p>
<div>Abstract<p>Allogeneic chimeric antigen receptor (CAR) T cell therapies hold the potential to overcome many of challenges associated with patient-derived (autologous) CAR cells. Key considerations in development allogeneic include prevention graft-vs-host disease (GvHD) and suppression allograft rejection. Here, we describe preclinical data supporting ongoing first-in-human clinical study, CaMMouflage trial (NCT05722418), evaluating CB-011 patients relapsed/refractory...
<p>CB-011 immune-cloaking armoring strategy reduced NK cell proliferation and CAR+ T stress signatures.</p>
<div>Abstract<p>Allogeneic chimeric antigen receptor (CAR) T cell therapies hold the potential to overcome many of challenges associated with patient-derived (autologous) CAR cells. Key considerations in development allogeneic include prevention graft-vs-host disease (GvHD) and suppression allograft rejection. Here, we describe preclinical data supporting ongoing first-in-human clinical study, CaMMouflage trial (NCT05722418), evaluating CB-011 patients relapsed/refractory...
<p>In vitro serial rechallenge assay demonstrates long-term cytotoxicity activity of CB-011 against BCMA+ tumor cells.</p>
<p>Antitumor activity of CB-011 CAR-T cells in a xenograft model multiple myeloma.</p>