Lipid Nanoparticle-Enabled Intracellular Delivery of Prime Editors

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Lipid Nanoparticle-Enabled Intracellular Delivery of Prime Editors. / Herrera-Barrera, Marco; Gautam, Milan; Lokras, Abhijeet; Vlasova, Kseniia; Foged, Camilla; Sahay, Gaurav.

In: The AAPS Journal, Vol. 25, No. 4, 65, 2023.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Herrera-Barrera, M, Gautam, M, Lokras, A, Vlasova, K, Foged, C & Sahay, G 2023, 'Lipid Nanoparticle-Enabled Intracellular Delivery of Prime Editors', The AAPS Journal, vol. 25, no. 4, 65. https://doi.org/10.1208/s12248-023-00833-2

APA

Herrera-Barrera, M., Gautam, M., Lokras, A., Vlasova, K., Foged, C., & Sahay, G. (2023). Lipid Nanoparticle-Enabled Intracellular Delivery of Prime Editors. The AAPS Journal, 25(4), [65]. https://doi.org/10.1208/s12248-023-00833-2

Vancouver

Herrera-Barrera M, Gautam M, Lokras A, Vlasova K, Foged C, Sahay G. Lipid Nanoparticle-Enabled Intracellular Delivery of Prime Editors. The AAPS Journal. 2023;25(4). 65. https://doi.org/10.1208/s12248-023-00833-2

Author

Herrera-Barrera, Marco ; Gautam, Milan ; Lokras, Abhijeet ; Vlasova, Kseniia ; Foged, Camilla ; Sahay, Gaurav. / Lipid Nanoparticle-Enabled Intracellular Delivery of Prime Editors. In: The AAPS Journal. 2023 ; Vol. 25, No. 4.

Bibtex

@article{fb989eeb38564a308306ae228c782200,

title = "Lipid Nanoparticle-Enabled Intracellular Delivery of Prime Editors",

abstract = "Prime editing is an advanced gene editing platform with potential to correct almost any disease-causing mutation. As genome editors have evolved, their size and complexity have increased, hindering delivery technologies with low-carrying capacity and endosomal escape. We formulated an array of lipid nanoparticles (LNPs) containing prime editors (PEs). We were able to encapsulate PEs in LNPs and confirmed the presence of PE mRNA and two different guide RNAs using HPLC. In addition, we developed a novel reporter cell line for rapid identification of LNPs suited for prime editing. A 54% prime editing rate was observed with enhanced LNPs (eLNPs) containing the cholesterol analog β-sitosterol at optimal ratios of RNA cargoes. eLNPs displayed a polyhedral morphology and a more fluid membrane state that led to improved endosomal escape, eventually causing onset of editing within 9 h and reaching maximum efficiency after 24 h. Hence, PEs delivered using LNPs can propel a new wave of therapies for many additional targets potentially enabling a range of new applications.",

author = "Marco Herrera-Barrera and Milan Gautam and Abhijeet Lokras and Kseniia Vlasova and Camilla Foged and Gaurav Sahay",

note = "{\textcopyright} 2023. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.",

year = "2023",

doi = "10.1208/s12248-023-00833-2",

language = "English",

volume = "25",

journal = "A A P S Journal",

issn = "1550-7416",

publisher = "Springer",

number = "4",

}

RIS

TY - JOUR

T1 - Lipid Nanoparticle-Enabled Intracellular Delivery of Prime Editors

AU - Herrera-Barrera, Marco

AU - Gautam, Milan

AU - Lokras, Abhijeet

AU - Vlasova, Kseniia

AU - Foged, Camilla

AU - Sahay, Gaurav

PY - 2023

Y1 - 2023

N2 - Prime editing is an advanced gene editing platform with potential to correct almost any disease-causing mutation. As genome editors have evolved, their size and complexity have increased, hindering delivery technologies with low-carrying capacity and endosomal escape. We formulated an array of lipid nanoparticles (LNPs) containing prime editors (PEs). We were able to encapsulate PEs in LNPs and confirmed the presence of PE mRNA and two different guide RNAs using HPLC. In addition, we developed a novel reporter cell line for rapid identification of LNPs suited for prime editing. A 54% prime editing rate was observed with enhanced LNPs (eLNPs) containing the cholesterol analog β-sitosterol at optimal ratios of RNA cargoes. eLNPs displayed a polyhedral morphology and a more fluid membrane state that led to improved endosomal escape, eventually causing onset of editing within 9 h and reaching maximum efficiency after 24 h. Hence, PEs delivered using LNPs can propel a new wave of therapies for many additional targets potentially enabling a range of new applications.

AB - Prime editing is an advanced gene editing platform with potential to correct almost any disease-causing mutation. As genome editors have evolved, their size and complexity have increased, hindering delivery technologies with low-carrying capacity and endosomal escape. We formulated an array of lipid nanoparticles (LNPs) containing prime editors (PEs). We were able to encapsulate PEs in LNPs and confirmed the presence of PE mRNA and two different guide RNAs using HPLC. In addition, we developed a novel reporter cell line for rapid identification of LNPs suited for prime editing. A 54% prime editing rate was observed with enhanced LNPs (eLNPs) containing the cholesterol analog β-sitosterol at optimal ratios of RNA cargoes. eLNPs displayed a polyhedral morphology and a more fluid membrane state that led to improved endosomal escape, eventually causing onset of editing within 9 h and reaching maximum efficiency after 24 h. Hence, PEs delivered using LNPs can propel a new wave of therapies for many additional targets potentially enabling a range of new applications.

U2 - 10.1208/s12248-023-00833-2

DO - 10.1208/s12248-023-00833-2

M3 - Journal article

C2 - 37380935

VL - 25

JO - A A P S Journal

JF - A A P S Journal

SN - 1550-7416

IS - 4

M1 - 65

ER -

ID: 357847503

Department of Pharmacy