A5075589378- CRISPR and Genetic Engineering
- Hemoglobinopathies and Related Disorders
- Advanced biosensing and bioanalysis techniques
- CAR-T cell therapy research
- HIV Research and Treatment
- Cytomegalovirus and herpesvirus research
- Mosquito-borne diseases and control
- RNA regulation and disease
- Pluripotent Stem Cells Research
- RNA and protein synthesis mechanisms
- Prenatal Screening and Diagnostics
- DNA and Nucleic Acid Chemistry
- Immunodeficiency and Autoimmune Disorders
- Virus-based gene therapy research
- Immune Cell Function and Interaction
- RNA Interference and Gene Delivery
Harvard University
2021-2023
Howard Hughes Medical Institute
2022-2023
Broad Institute
2020-2023
Prime editing enables a wide variety of precise genome edits in living cells. Here we use protein evolution and engineering to generate prime editors with reduced size improved efficiency. Using phage-assisted evolution, efficiencies compact reverse transcriptases by up 22-fold generated that are 516–810 base pairs smaller than the current-generation editor PEmax. We discovered different specialize types used this insight outperform PEmax PEmaxΔRNaseH, truncated dual-AAV delivery systems....
Sickle-cell disease (SCD) is caused by an A·T-to-T·A transversion mutation in the β-globin gene (HBB). Here we show that prime editing can correct SCD allele (HBB
Sickle Cell Disease (SCD) is a monogenic disease caused by nucleotide mutation in the β-globin gene. Current gene therapy studies are mainly focused on lentivirus vector-mediated addition or CRISPR/Cas9-mediated fetal globin reactivation, leaving root cause unfixed. We developed vectorized prime editing system that can directly repair SCD hematopoietic stem cells (HSCs) vivo mouse model (CD46/Townes mice). Our approach involved single intravenous injection of non-integrating,...
Individuals with β-thalassemia or sickle cell disease and hereditary persistence of fetal hemoglobin (HPFH) possessing 30% (HbF) appear to be symptom free. Here, we used a nonintegrating HDAd5/35++ vector expressing highly efficient accurate version an adenine base editor (ABE8e) install, in vivo, -113 A>G HPFH mutation the γ-globin promoters healthy CD46/β-YAC mice carrying human β-globin locus. Our vivo hematopoietic stem (HSC) editing/selection strategy involves only s.c. i.v. injections...