A5043393398- Virus-based gene therapy research
- CRISPR and Genetic Engineering
- Cytomegalovirus and herpesvirus research
- CAR-T cell therapy research
- HIV Research and Treatment
- Cystic Fibrosis Research Advances
- Energy Harvesting in Wireless Networks
- Viral Infections and Immunology Research
- RNA Interference and Gene Delivery
- Immune Cell Function and Interaction
- Advanced biosensing and bioanalysis techniques
- Pluripotent Stem Cells Research
- RNA modifications and cancer
- HIV/AIDS drug development and treatment
- Herpesvirus Infections and Treatments
- Cardiac Structural Anomalies and Repair
- Respiratory viral infections research
- Mechanical Circulatory Support Devices
- Viral Infectious Diseases and Gene Expression in Insects
- Nuclear Structure and Function
- RNA Research and Splicing
Stanford University
2019-2025
California Institute for Regenerative Medicine
2023
Harvard University
2018-2019
Massachusetts Eye and Ear Infirmary
2018-2019
Smith-Kettlewell Eye Research Institute
2018-2019
Dana-Farber Cancer Institute
2019
Innovative Genomics Institute
2018
Adeno-associated virus (AAV) is a highly promising gene transfer vector, yet major cellular requirements for AAV entry are poorly understood. Using genome-wide CRISPR screen of evolutionarily divergent serotype AAVrh32.33, we identified GPR108, member the G protein-coupled receptor superfamily, as an factor. Of greater than 20 AAVs across all clades tested in human cell lines, only AAV5 transduction was unaffected GPR108 knockout (KO). dependency further shown murine and primary cells vitro....
ABSTRACT Determinants and mechanisms of cell attachment entry steer adeno-associated virus (AAV) in its utility as a gene therapy vector. Thus far, systematic assessment how diverse AAV serotypes engage their proteinaceous receptor AAVR (KIAA0319L) to establish transduction has been lacking, despite potential implications for tissue tropism. Here, large set human simian AAVs well silico -reconstructed ancestral capsids were interrogated usage. We identified distinct capsid lineage comprised...
Abstract Genome editing by homology directed repair (HDR) is leveraged to precisely modify the genome of therapeutically relevant hematopoietic stem and progenitor cells (HSPCs). Here, we present a new approach increasing frequency HDR in human HSPCs delivery an inhibitor 53BP1 (named “i53”) as recombinant peptide. We show that use i53 peptide effectively increases HDR-mediated at variety loci well other primary cell types. incorporating protein allows high frequencies while lowering amounts...
Cystic fibrosis (CF) is a monogenic disease caused by impaired production and/or function of the CF transmembrane conductance regulator (CFTR) protein. Although we have previously shown correction most common pathogenic mutation, there are many other mutations throughout gene. An autologous airway stem cell therapy in which CFTR cDNA precisely inserted into locus may enable development durable cure for almost all patients, irrespective causal mutation. Here, use CRISPR-Cas9 and two...
Cleavage factor I mammalian (CFIm) complex, composed of cleavage and polyadenylation specificity 5 (CPSF5) serine/arginine-like protein CPSF6, regulates alternative (APA). Loss CFIm function results in proximal site usage, shortening mRNA 3′ untranslated regions (UTRs). Although CPSF6 plays additional roles human disease, its nuclear translocation mechanism remains unresolved. Two β-karyopherins, transportin (TNPO) 1 TNPO3, can bind vitro, we demonstrate here that while the TNPO1 binding is...
In vivo gene therapy targeting hematopoietic stem cells (HSCs) holds significant therapeutic potential for treating hematological diseases. This study uses adeno-associated virus serotype 6 (AAV6) vectors and Cre recombination to systematically optimize the parameters effective in HSC transduction. We evaluated various genetic architectures delivery methods of AAV6, establishing an optimized protocol that achieved functional more than two-thirds immunophenotypic HSCs. Our findings highlight...
Allogeneic transplantation of CCR5 null hematopoietic stem and progenitor cells (HSPCs) is the only known cure for HIV-1 infection. However, this treatment limited because rarity CCR5-null matched donors, morbidities associated with allogeneic transplantation, prevalence strains resistant to knockout (KO) alone. Here, we propose a one-time therapy through autologous HSPCs genetically engineered ex vivo produce both KO long-term secretion potent inhibiting antibodies from B cell progeny....
Abstract Canonical HIV-1 entry into target cells depends on binding to CD4 as a primary receptor. Because of this, use the receptor viral trap (a decoy used prevent infection cells) is promising strategy for treatment HIV-1. One challenge in using traps maintaining enough circulation remain effective. Here we present produce cell-based by engineering hematopoietic stem and progenitor (HSPCs) express red blood cell (RBC) progeny. This takes advantage ability HSPC repopulate system lifetime,...
Abstract Cystic fibrosis (CF) is a monogenic disease caused by impaired production and/or function of the cystic transmembrane conductance regulator (CFTR) protein. Although we have previously shown correction most common pathogenic mutation, there are many other mutations throughout CF gene. An autologous airway stem cell therapy in which CFTR cDNA precisely inserted into locus may enable development durable cure for almost all patients, irrespective causal mutation. Here, use CRISPR/Cas9...
Abstract Autologous transplantation of CCR5 null hematopoietic stem and progenitor cells (HSPCs) is the only known cure for HIV-1 infection. However, this treatment limited because rarity -null matched donors, morbidities associated with allogeneic transplantation, prevalence strains resistant to knockout (KO) alone. Here, we propose a one-time therapy through autologous HSPCs genetically engineered ex vivo produce both KO long-term secretion potent inhibiting antibodies from B cell progeny....
Abstract Genome editing by homology directed repair (HDR) is leveraged to precisely modify the genome of therapeutically relevant hematopoietic stem and progenitor cells (HSPCs). Here, we present a new approach increasing frequency HDR in human HSPCs delivery i53 recombinant protein. We show that use peptide effectively increases HDR-mediated at variety loci as well other primary cell types. incorporating protein allows high levels be attained while lowering amounts AAV6 needed 8-fold....
Download This Paper Open PDF in Browser Add to My Library Share: Permalink Using these links will ensure access this page indefinitely Copy URL DOI