Process for production of chimeric antigen receptor-transducing lentivirus particles using infection with replicon particles containing self-replicating RNAs
Syzdykova L. Zauatbayeva G. Keyer V. Ramanculov Y. Arsienko R. Shustov A.V.
February 2023Elsevier B.V.
Biochemical Engineering Journal
2023#191
Viral vectors are indispensable for advanced therapeutics such as chimeric T cell antigen receptor (CAR-T) therapy. CAR-T is a revolutionary treatment for blood cancers in patients who have relapsed or refractory disease after standard therapy. The therapeutic success is driving CAR-Ts wider adoption, but the prospects for wider use are currently limited by high price, including the price of a packaged CAR vector, and the limited supply of such a vector on the market. The production of large quantities of packaged lentiviral vector using transfection with multiple plasmids in academic settings is associated with technical difficulties. Here we describe a technology for packaging a lentiviral vector using autonomously replicating RNAs that are delivered to production cultures by infection with replicon particles. Chimeric vectors capable of cytoplasmic replication were assembled using a replicative backbone from the RNA-virus Venezuelan equine encephalitis virus, into which the HIV-1 sequences for genomic integration and the CAR transgene were cloned. These vectors are packaged into high-titered infectious alphavirus replicon particles, allowing subsequent infection of large culture volumes to produce lentivirus particles. Using this method, enough vector was generated to produce therapeutic amounts of CAR+ cells in an academic setting.
Autonomously replicating RNA , CAR-T therapy , Chimeric antigen receptor , Lentivirus vector packaging , Replicon particle
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National Center for Biotechnology, Nur-Sultan, 010000, Kazakhstan
S.D. Asfendiyarov Kazakh National Medical University, Almaty, 050000, Kazakhstan
National Center for Biotechnology
S.D. Asfendiyarov Kazakh National Medical University
10 лет помогаем публиковать статьи Международный издатель
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