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Vectorology - GEG Tech top picks
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BigField GEG Tech's insight:
Cancer immunotherapy using T cells engineered ex vivo with a chimeric antigen receptor (CAR) against CD19 is currently facing major breakthroughs in the treatment of B-cell malignancies. Successful therapeutic outcome depends on long-term expression of CAR transgene in T cells, which is achieved by delivering transgene using integrating gamma retrovirus (RV) or lentivirus (LV). However, uncontrolled RV/LV integration in host cell genomes has the potential risk of causing insertional mutagenesis. In this work, the authors have designed an episomal long-term cell engineering method using non-integrating lentiviral (NILV) vector containing a scaffold/matrix attachment region (S/MAR) element. After 12 days of T-cell expansion, the scientists found that LV(CD19CAR)- and NILV-S/MAR(CD19CAR)-transduced T cells retained similar levels of CAR expression as before expansion. To meet clinical requirements, the efficacy of NILV-S/MAR (CD19CAR)-engineered T cells to control tumor growth was examined in a xenograft mouse model with Karpas 422 tumors. Mice treated with NILV-S/MAR(CD19CAR)-engineered T cells or LV(CD19CAR)-engineered T cells exhibited similarly suppressed tumor growth. The survival of tumor-bearing mice was significantly prolonged when treated with CD19 CAR T cells compared to mock T cells Taken together, the data suggest that the therapeutic efficacy of NILV-S/MAR-engineered CD19 CAR T cells is similar to that of T cells engineered with a self-inactivating integrating LV vector. GEG Tech R&D develops also smart designs of lentiviral vectors for a safe and efficient delivery of CAR through Lenti-ONE Epi and Lenti-ONE Trans vectors.
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To know more about Lenti-ONE & CAR T cells
To know more about Lenti-ONE Epi & Trans 
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BigField GEG Tech's insight:
The miniMAR variant of the human β-interferon S/MAR induces stable expression of non integrating lentiviral vector in dividing cells. Interesting element in gene transfer field!
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Safe and efficient gene transfer systems are the basis of gene therapy applications. Non-integrating lentiviral (NIL) vectors are among the most promising candidates for gene transfer tools, because t
BigField GEG Tech's insight:
In this work, the authors report the design of a non-integrating lentiviral vector that contains the minimal scaffold/matrix attachment region (S/MAR) sequence (SNIL), and this SNIL vector is able to retain episomal transgene expression in dividing cells. Using SNIL vectors, they detected the expression of the eGFP gene for 61 days in SNIL-transduced stable CHO cells, either with selection or not.
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BigField GEG Tech's insight:
Non integrating lentiviral vectors with mini MAR generating mitotically stable episomes capable of long-term transgene expression. 13-45% of cells expressing the transgene for over 100 cell generations in the absence of selection, great!
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Integration-defective lentiviral vectors (IDLVs) have become an important alternative
tool for gene therapy applications and basic research. Unfortunately, IDLVs show lower
transgene expression as compared to their integrating counterparts. In this study,
we aimed to improve the expression levels of IDLVs by inserting the IS2 element, which
harbors SARs and HS4 sequences, into their LTRs (SE-IS2-IDLVs). Contrary to our expectations,
the presence of the IS2 element did not abrogate epigenetic silencing by histone deacetylases.