In vivo CRISPR base editing of PCSK9 durably lowers cholesterol in primates
K Musunuru, AC Chadwick, T Mizoguchi, SP Garcia… - Nature, 2021 - nature.com
Gene-editing technologies, which include the CRISPR–Cas nucleases 1, 2, 3 and CRISPR
base editors 4, 5, have the potential to permanently modify disease-causing genes in …
base editors 4, 5, have the potential to permanently modify disease-causing genes in …
Efficacy and Safety of an Investigational Single-Course CRISPR Base-Editing Therapy Targeting PCSK9 in Nonhuman Primate and Mouse Models
RG Lee, AM Mazzola, MC Braun, C Platt, SB Vafai… - Circulation, 2023 - Am Heart Assoc
Background: VERVE-101 is an investigational in vivo CRISPR base-editing medicine
designed to alter a single DNA base in the PCSK9 gene, permanently turn off hepatic …
designed to alter a single DNA base in the PCSK9 gene, permanently turn off hepatic …
In utero CRISPR-mediated therapeutic editing of metabolic genes
AC Rossidis, JD Stratigis, AC Chadwick, HA Hartman… - Nature medicine, 2018 - nature.com
In utero gene editing has the potential to prenatally treat genetic diseases that result in
significant morbidity and mortality before or shortly after birth. We assessed the viral vector …
significant morbidity and mortality before or shortly after birth. We assessed the viral vector …
CRISPR-Cas9 Targeting of PCSK9 in Human Hepatocytes In Vivo—Brief Report
Objective—Although early proof-of-concept studies of somatic in vivo genome editing of the
mouse ortholog of proprotein convertase subtilisin/kexin type 9 (Pcsk9) in mice have …
mouse ortholog of proprotein convertase subtilisin/kexin type 9 (Pcsk9) in mice have …
Permanent alteration of PCSK9 with in vivo CRISPR-Cas9 genome editing
Q Ding, A Strong, KM Patel, SL Ng, BS Gosis… - Circulation …, 2014 - Am Heart Assoc
Rationale: Individuals with naturally occurring loss-of-function proprotein convertase
subtilisin/kexin type 9 (PCSK9) mutations experience reduced low-density lipoprotein …
subtilisin/kexin type 9 (PCSK9) mutations experience reduced low-density lipoprotein …
Meganuclease targeting of PCSK9 in macaque liver leads to stable reduction in serum cholesterol
Clinical translation of in vivo genome editing to treat human genetic diseases requires
thorough preclinical studies in relevant animal models to assess safety and efficacy. A …
thorough preclinical studies in relevant animal models to assess safety and efficacy. A …
In vivo genome and base editing of a human PCSK9 knock-in hypercholesterolemic mouse model
A Carreras, LS Pane, R Nitsch, K Madeyski-Bengtson… - BMC biology, 2019 - Springer
Background Plasma concentration of low-density lipoprotein (LDL) cholesterol is a well-
established risk factor for cardiovascular disease. Inhibition of proprotein convertase …
established risk factor for cardiovascular disease. Inhibition of proprotein convertase …
In vivo adenine base editing of PCSK9 in macaques reduces LDL cholesterol levels
T Rothgangl, MK Dennis, PJC Lin, R Oka… - Nature …, 2021 - nature.com
Most known pathogenic point mutations in humans are C• G to T• A substitutions, which can
be directly repaired by adenine base editors (ABEs). In this study, we investigated the …
be directly repaired by adenine base editors (ABEs). In this study, we investigated the …
Structure-guided chemical modification of guide RNA enables potent non-viral in vivo genome editing
Efficient genome editing with Cas9–sgRNA in vivo has required the use of viral delivery
systems, which have limitations for clinical applications. Translational efforts to develop …
systems, which have limitations for clinical applications. Translational efforts to develop …
CRISPR-Cas12a delivery by DNA-mediated bioresponsive editing for cholesterol regulation
CRISPR-Cas12a represents an efficient tool for genome editing in addition to the
extensively investigated CRISPR-Cas9. However, development of efficient nonviral delivery …
extensively investigated CRISPR-Cas9. However, development of efficient nonviral delivery …