Display options
Cite
Han J, Tam K, Tam C, et al. Improved lentiviral vector titers from a multi-gene knockout packaging line. Mol Ther Oncolytics. 2021;23:582-592doi: 10.1016/j.omto.2021.11.012.
Han, J., Tam, K., Tam, C., Hollis, R. P., & Kohn, D. B. (2021). Improved lentiviral vector titers from a multi-gene knockout packaging line. Molecular therapy oncolytics, 23582-592. https://doi.org/10.1016/j.omto.2021.11.012
Han, Jiaying, et al. "Improved lentiviral vector titers from a multi-gene knockout packaging line." Molecular therapy oncolytics vol. 23 (2021): 582-592. doi: https://doi.org/10.1016/j.omto.2021.11.012
Han J, Tam K, Tam C, Hollis RP, Kohn DB. Improved lentiviral vector titers from a multi-gene knockout packaging line. Mol Ther Oncolytics. 2021 Nov 20;23:582-592. doi: 10.1016/j.omto.2021.11.012. eCollection 2021 Dec 17. PMID: 34938858; PMCID: PMC8660686.
Copy Download .nbib Format: NLM
Share it on

Mol Ther Oncolytics. 2021 Nov 20;23:582-592. doi: 10.1016/j.omto.2021.11.012. eCollection 2021 Dec 17.

Improved lentiviral vector titers from a multi-gene knockout packaging line.

Molecular therapy oncolytics

Jiaying Han, Kevin Tam, Curtis Tam, Roger P Hollis, Donald B Kohn

Affiliations

  1. Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
  2. Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, CA 90095, USA.
  3. Department of Microbiology, Immunology & Molecular Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
  4. Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
  5. The Eli & Edythe Broad Center of Regenerative Medicine & Stem Cell Research, University of California, Los Angeles, CA 90095, USA.
  6. UCLA Jonsson Comprehensive Cancer Center, Los Angeles, CA 90095, USA.

PMID: 34938858 PMCID: PMC8660686 DOI: 10.1016/j.omto.2021.11.012

Abstract

Lentiviral vectors (LVs) are robust delivery vehicles for gene therapy as they can efficiently integrate transgenes into host cell genomes. However, LVs with lengthy or complex expression cassettes typically are produced at low titers and have reduced gene transfer capacity, creating barriers for clinical and commercial applications. Modifications of the packaging cell line and methods may be able to produce complex vectors at higher titer and infectivity and may improve production of many different LVs. In this study, we identified two host restriction factors in HEK293T packaging cells that impeded LV production, 2'-5'-oligoadenylate synthetase 1 (OAS1) and low-density lipoprotein receptor (LDLR). Knocking out these two genes separately led to ∼2-fold increases in viral titer. We created a monoclonal cell line, CRISPRed HEK293T to Disrupt Antiviral Response (CHEDAR), by successively knocking out

© 2021 The Authors.

Keywords: CAR-T; HEK293T cells; gene and cell therapy; hemoglobinopathy; lentiviral vector; packaging

Conflict of interest statement

The authors declare no competing interests.

Publication Types