Enhancing Lentiviral Vector Transduction Efficiency for Facilitating Gene Therapy

doi:10.13523/j.cb.2104039

China Biotechnology

2021, Vol. 41

Issue (8): 52-58 DOI: 10.13523/j.cb.2104039

Enhancing Lentiviral Vector Transduction Efficiency for Facilitating Gene Therapy

ZHAO Xiao-yu¹,XU Qi-ling^1,²,ZHAO Xiao-dong^2,^3,^4,^5,^**(

),AN Yun-fei^1,^2,^3,^4,⁵

1 Department of Rheumatology and Immunology, Affiliated Children's Hospital of Chongqing Medical University, Chongqing 400014, China
2 Chongqing Key Laboratory of Children's Infection and Immunity, Chongqing 400014, China
3 Key Laboratory of Children's Developmental Diseases, Ministry of Education, Chongqing 400014, China
4 National Children's Health and Disease Clinical Medical Research Center (Chongqing), Chongqing 400014, China
5 National International Science and Technology Cooperation Base for Major Children's Developmental Diseases, Chongqing 400014, China

Download:

HTML

PDF(998KB) HTML
Export: BibTeX | EndNote (RIS)

Abstract

Lentiviral vectors (LVVs) are used for various gene therapeutic applications in vitro, and have shown very promising results in several clinical trials. This possibility of a durable cure for monogenic diseases affecting the hematopoietic system has made gene therapy very attractive. Yet, efficiency, safety, and cost of LVVs gene therapy could be ameliorated by enhancing target cell transduction levels and reducing the amount of LVVs used on the cells. LVVs are pseudotyped with different viral envelope glycoproteins to alter and improve their tropism for different target cells. Another strategy to optimize the entry and post-entry steps of LVVs is the addition of transduction enhancers (TEs) during the transduction procedure, which improves the transduction efficiency and keeps stable expression of transferred genes in vivo. The combination of pseudotyping with heterologous viral envelopes and adding TEs increased the transduction efficiency of LVVs, and has the potential to improve clinical protocols.

Key words： Gene therapy Transduction efficiency Lentiviral vectors Envelope glycoprotein Viral transduction enhancer

Received: 22 April 2021 Published: 31 August 2021

ZTFLH:

Q812

Corresponding Authors: Xiao-dong ZHAO E-mail: zhaoxd530@aliyun.com

	Service
	E-mail this article
	Add to my bookshelf
	Add to citation manager
	E-mail Alert
	RSS
	Articles by authors
	Xiao-yu ZHAO
	Qi-ling XU
	Xiao-dong ZHAO
	Yun-fei AN

Cite this article:

ZHAO Xiao-yu,XU Qi-ling,ZHAO Xiao-dong,AN Yun-fei. Enhancing Lentiviral Vector Transduction Efficiency for Facilitating Gene Therapy. China Biotechnology, 2021, 41(8): 52-58.

URL:

https://manu60.magtech.com.cn/biotech/10.13523/j.cb.2104039 OR https://manu60.magtech.com.cn/biotech/Y2021/V41/I8/52


[1]	Odiba A S, Okoro N O, Durojaye O A, et al. Gene therapy in PIDs, hemoglobin, ocular, neurodegenerative, and hemophilia B disorders. Open Life Sciences, 2021, 16(1):431-441. doi: 10.1515/biol-2021-0033

[2]	Hacein-Bey-abina S, Garrigue A, Wang G P, et al. Insertional oncogenesis in 4 patients after retrovirus-mediated gene therapy of SCID-X1. The Journal of Clinical Investigation, 2008, 118(9):3132-3142. doi: 10.1172/JCI35700

[3]	Hacein-Bey-abina S, Hauer J, Lim A, et al. Efficacy of gene therapy for X-linked severe combined immunodeficiency. New England Journal of Medicine, 2010, 363(4):355-364. doi: 10.1056/NEJMoa1000164

[4]	Mamcarz E, Zhou S, Lockey T, et al. Lentiviral gene therapy combined with low-dose busulfan in infants with SCID-X1. The New England Journal of Medicine, 2019, 380(16):1525-1534. doi: 10.1056/NEJMoa1815408

[5]	Kohn D B, Booth C, Kang E M, et al. Lentiviral gene therapy for X-linked chronic granulomatous disease. Nature Medicine, 2020, 26(2):200-206. doi: 10.1038/s41591-019-0735-5

[6]	Thompson A A, Walters M C, Kwiatkowski J, et al. Gene therapy in patients with transfusion-dependent β-thalassemia. The New England Journal of Medicine, 2018, 378(16):1479-1493. doi: 10.1056/NEJMoa1705342 pmid: 29669226

[7]	de Ravin S S, Wu X L, Moir S, et al. Lentiviral hematopoietic stem cell gene therapy for X-linked severe combined immunodeficiency. Science Translational Medicine, 2016, 8(335): 335ra57.

[8]	Millington M, Arndt A, Boyd M, et al. Towards a clinically relevant lentiviral transduction protocol for primary human CD34 hematopoietic stem/progenitor cells. PLoS One, 2009, 4(7):e6461. doi: 10.1371/journal.pone.0006461

[9]	Gutierrez-Guerrero A, Cosset F L, Verhoeyen E. Lentiviral vector pseudotypes: precious tools to improve gene modification of hematopoietic cells for research and gene therapy. Viruses, 2020, 12(9):1016. doi: 10.3390/v12091016

[10]	Anastasov N, Höfig I, Mall S, et al. Optimized lentiviral transduction protocols by use of a poloxamer enhancer, spinoculation, and scFv-antibody fusions to VSV-G. Lentiviral Vectors and Exosomes as Gene and Protein Delivery Tools, 2016: 1448:49-61. DOI: 10.1007/978-1-4939-3753-0_4. doi: 10.1007/978-1-4939-3753-0_4

[11]	Amirache F, Lévy C, Costa C, et al. Mystery solved: VSV-G-LVs do not allow efficient gene transfer into unstimulated T cells, B cells, and HSCs because they lack the LDL receptor. Blood, 2014, 123(9):1422-1424. doi: 10.1182/blood-2013-11-540641 pmid: 24578496

[12]	Ahmed F, Ings S J, Pizzey A R, et al. Impaired bone marrow homing of cytokine-activated CD34+ cells in the NOD/SCID model. Blood, 2004, 103(6):2079-2087. doi: 10.1182/blood-2003-06-1770

[13]	Di Nunzio F, Piovani B, Cosset F L, et al. Transduction of human hematopoietic stem cells by lentiviral vectors pseudotyped with the RD114-TR chimeric envelope glycoprotein. Human Gene Therapy, 2007, 18(9):811-820. pmid: 17824830

[14]	Girard-Gagnepain A, Amirache F, Costa C, et al. Baboon envelope pseudotyped LVs outperform VSV-G-LVs for gene transfer into early-cytokine-stimulated and resting HSCs. Blood, 2014, 124(8):1221-1231. doi: 10.1182/blood-2014-02-558163 pmid: 24951430

[15]	Marin M, Lavillette D, Kelly S M, et al. N-linked glycosylation and sequence changes in a critical negative control region of the ASCT1 and ASCT2 neutral amino acid transporters determine their retroviral receptor functions. Journal of Virology, 2003, 77(5):2936-2945. doi: 10.1128/JVI.77.5.2936-2945.2003

[16]	Bernadin O, Amirache F, Girard-Gagnepain A, et al. Baboon envelope LVs efficiently transduced human adult, fetal, and progenitor T cells and corrected SCID-X1 T-cell deficiency. Blood Advances, 2019, 3(3):461-475. doi: 10.1182/bloodadvances.2018027508

[17]	Colamartino A B L, Lemieux W, Bifsha P, et al. Efficient and robust NK-cell transduction with baboon envelope pseudotyped lentivector. Frontiers in Immunology, 2019, 10:2873. doi: 10.3389/fimmu.2019.02873 pmid: 31921138

[18]	Frecha C, Levy C, Costa C, et al. Measles virus glycoprotein-pseudotyped lentiviral vector-mediated gene transfer into quiescent lymphocytes requires binding to both SLAM and CD46 entry receptors. Journal of Virology, 2011, 85(12):5975-5985. doi: 10.1128/JVI.00324-11

[19]	Frecha C, Costa C, Nègre D, et al. Stable transduction of quiescent T cells without induction of cycle progression by a novel lentiviral vector pseudotyped with measles virus glycoproteins. Blood, 2008, 112(13):4843-4852.

[20]	Lévy C, Amirache F, Girard-Gagnepain A, et al. Measles virus envelope pseudotyped lentiviral vectors transduce quiescent human HSCs at an efficiency without precedent. Blood Advances, 2017, 1(23):2088-2104. doi: 10.1182/bloodadvances.2017007773

[21]	DePolo N J, Reed J D, Sheridan P L, et al. VSV-G pseudotyped lentiviral vector particles produced in human cells are inactivated by human serum. Molecular Therapy, 2000, 2(3):218-222. pmid: 10985952

[22]	Humbert O, Gisch D W, Wohlfahrt M E, et al. Development of third-generation cocal envelope producer cell lines for robust lentiviral gene transfer into hematopoietic stem cells and T-cells. Molecular Therapy, 2016, 24(7):1237-1246. doi: 10.1038/mt.2016.70

[23]	Hu S, Mohan Kumar D, Sax C, et al. Pseudotyping of lentiviral vector with novel Vesiculovirus envelope glycoproteins derived from Chandipura and Piry viruses. Virology, 2016, 488:162-168. doi: 10.1016/j.virol.2015.11.012

[24]	Cornetta K, Anderson W F. Protamine sulfate as an effective alternative to polybrene in retroviral-mediated gene-transfer: implications for human gene therapy. Journal of Virological Methods, 1989, 23(2):187-194. pmid: 2786000

[25]	Davis H E, Morgan J R, Yarmush M L. Polybrene increases retrovirus gene transfer efficiency by enhancing receptor-independent virus adsorption on target cell membranes. Biophysical Chemistry, 2002, 97(2-3):159-172. doi: 10.1016/S0301-4622(02)00057-1

[26]	Lin P, Correa D, Lin Y, et al. Polybrene inhibits human mesenchymal stem cell proliferation during lentiviral transduction. PLoS One, 2011, 6(8):e23891. DOI: 10.1371/journal.pone.0023891. doi: 10.1371/journal.pone.0023891

[27]	Nanba D, Matsushita N, Toki F, et al. Efficient expansion of human keratinocyte stem/progenitor cells carrying a transgene with lentiviral vector. Stem Cell Research & Therapy, 2013, 4(5):127.

[28]	Han M M, Yu D Z, Song Q, et al. Polybrene: Observations on cochlear hair cell necrosis and minimal lentiviral transduction of cochlear hair cells. Neuroscience Letters, 2015, 600:164-170. doi: 10.1016/j.neulet.2015.06.011

[29]	Kim B J, Kim K J, Kim Y H, et al. Efficient enhancement of lentiviral transduction efficiency in murine spermatogonial stem cells. Molecules and Cells, 2012, 33(5):449-455. doi: 10.1007/s10059-012-2167-7

[30]	Zhou R Q, Gong Y P, Lin J, et al. The optimization of method for lentiviral vector to transfect CD34+ hematopoietic stem cells from human cord. Journal of Sichuan University Medical Science Edition, 2013, 44(1):130-134.

[31]	Lin P, Lin Y, Lennon D P, et al. Efficient lentiviral transduction of human mesenchymal stem cells that preserves proliferation and differentiation capabilities. Stem Cells Translational Medicine, 2012, 1(12):886-897. doi: 10.5966/sctm.2012-0086

[32]	Hauber I, Beschorner N, Schrödel S, et al. Improving lentiviral transduction of CD34+ hematopoietic stem and progenitor cells. Human Gene Therapy Methods, 2018, 29(2):104-113. doi: 10.1089/hgtb.2017.085

[33]	Delville M, Soheili T, Bellier F, et al. A nontoxic transduction enhancer enables highly efficient lentiviral transduction of primary murine T cells and hematopoietic stem cells. Molecular Therapy - Methods & Clinical Development, 2018, 10:341-347.

[34]	Kerkar S P, Sanchez-Perez L, Yang S C, et al. Genetic engineering of murine CD8+ and CD4+ T cells for preclinical adoptive immunotherapy studies. Journal of Immunotherapy, 2011, 34(4):343-352. doi: 10.1097/CJI.0b013e3182187600 pmid: 21499127

[35]	Elias A K, Scanlon D, Musgrave I F, et al. SEVI, the semen enhancer of HIV infection along with fragments from its central region, form amyloid fibrils that are toxic to neuronal cells. Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, 2014, 1844(9):1591-1598. doi: 10.1016/j.bbapap.2014.06.006

[36]	Roan N R, Münch J, Arhel N, et al. The cationic properties of SEVI underlie its ability to enhance human immunodeficiency virus infection. Journal of Virology, 2009, 83(1):73-80. doi: 10.1128/JVI.01366-08

[37]	Wurm M, Schambach A, Lindemann D, et al. The influence of semen-derived enhancer of virus infection on the efficiency of retroviral gene transfer. The Journal of Gene Medicine, 2010, 12(2):137-146.

[38]	Wurm M, Gross B, Sgodda M, et al. Improved lentiviral gene transfer into human embryonic stem cells grown in co-culture with murine feeder and stroma cells. Biological Chemistry, 2011, 392(10):887-895. doi: 10.1515/BC.2011.085

[39]	Höfig I, Atkinson M J, Mall S, et al. Poloxamer synperonic F108 improves cellular transduction with lentiviral vectors. The Journal of Gene Medicine, 2012, 14(8):549-560. doi: 10.1002/jgm.2653 pmid: 22887595

[40]	Simon B, Harrer D C, Thirion C, et al. Enhancing lentiviral transduction to generate melanoma-specific human T cells for cancer immunotherapy. Journal of Immunological Methods, 2019, 472:55-64. doi: 10.1016/j.jim.2019.06.015

[41]	North T E, Goessling W, Walkley C R, et al. Prostaglandin E2 regulates vertebrate haematopoietic stem cell homeostasis. Nature, 2007, 447(7147):1007-1011. doi: 10.1038/nature05883

[42]	Goessling W, Allen R S, Guan X, et al. Prostaglandin E2 enhances human cord blood stem cell xenotransplants and shows long-term safety in preclinical nonhuman primate transplant models. Cell Stem Cell, 2011, 8(4):445-458. doi: 10.1016/j.stem.2011.02.003 pmid: 21474107

[43]	Zonari E, Desantis G, Petrillo C, et al. Efficient ex vivo engineering and expansion of highly purified human hematopoietic stem and progenitor cell populations for gene therapy. Stem Cell Reports, 2017, 8(4):977-990. doi: S2213-6711(17)30077-2 pmid: 28330619

[44]	Cutler C, Multani P, Robbins D, et al. Prostaglandin-modulated umbilical cord blood hematopoietic stem cell transplantation. Blood, 2013, 122(17):3074-3081. doi: 10.1182/blood-2013-05-503177 pmid: 23996087

[45]	Brown B D, Sitia G, Annoni A, et al. In vivo administration of lentiviral vectors triggers a type I interferon response that restricts hepatocyte gene transfer and promotes vector clearance. Blood, 2007, 109(7):2797-2805. doi: 10.1182/blood-2006-10-049312

[46]	Yan N, Chen Z J. Intrinsic antiviral immunity. Nature Immunology, 2012, 13(3):214-222. doi: 10.1038/ni.2229

[47]	Petrillo C, Calabria A, Piras F, et al. Assessing the impact of cyclosporin A on lentiviral transduction and preservation of human hematopoietic stem cells in clinically relevant ex vivo gene therapy settings. Human Gene Therapy, 2019, 30(9):1133-1146. doi: 10.1089/hum.2019.016

[48]	Petrillo C, Cesana D, Piras F, et al. Cyclosporin A and rapamycin relieve distinct lentiviral restriction blocks in hematopoietic stem and progenitor cells. Molecular Therapy, 2015, 23(2):352-362. doi: 10.1038/mt.2014.193

[49]	Amini-Bavil-olyaee S, Choi Y J, Lee J H, et al. The antiviral effector IFITM3 disrupts intracellular cholesterol homeostasis to block viral entry. Cell Host & Microbe, 2013, 13(4):452-464.

[50]	Smith S, Weston S, Kellam P, et al. IFITM proteins-cellular inhibitors of viral entry. Current Opinion in Virology, 2014, 4:71-77. doi: 10.1016/j.coviro.2013.11.004 pmid: 24480526

[51]	Li K, Markosyan R M, Zheng Y M, et al. IFITM proteins restrict viral membrane hemifusion. PLoS Pathogens, 2013, 9(1):e1003124. DOI: 10.1371/journal.ppat.1003124. doi: 10.1371/journal.ppat.1003124

[52]	Chan Y K, Huang I C, Farzan M. IFITM proteins restrict antibody-dependent enhancement of dengue virus infection. PLoS One, 2012, 7(3):e34508. DOI: 10.1371/journal.pone.0034508. doi: 10.1371/journal.pone.0034508

[53]	Wu X F, Dao Thi V L, Huang Y M, et al. Intrinsic immunity shapes viral resistance of stem cells. Cell, 2018, 172(3):423-438.e25. doi: 10.1016/j.cell.2017.11.018

[54]	Petrillo C, Thorne L G, Unali G, et al. Cyclosporine H overcomes innate immune restrictions to improve lentiviral transduction and gene editing in human hematopoietic stem cells. Cell Stem Cell, 2018, 172(3):423-438.e25.

[55]	Jang Y, Kim Y S, Wielgosz M M, et al. Optimizing lentiviral vector transduction of hematopoietic stem cells for gene therapy. Gene Therapy, 2020, 27(12):545-556. doi: 10.1038/s41434-020-0150-z

[56]	Olender L, Bujanover N, Sharabi O, et al. 3119 - cyclosporine h improves the multi-vector lentiviral transduction of murine haematopoietic progenitors and stem cells. Experimental Hematology, 2020, 88:S75.

[57]	Piras F, Riba M, Petrillo C, et al. Lentiviral vectors escape innate sensing but trigger p53 in human hematopoietic stem and progenitor cells. EMBO Molecular Medicine, 2017, 9(9):1198-1211. doi: 10.15252/emmm.201707922

[58]	Biffi A, Montini E, Lorioli L, et al. Lentiviral hematopoietic stem cell gene therapy benefits metachromatic leukodystrophy. Science, 2013, 341(6148):1233158. doi: 10.1126/science.1233158

[59]	Aiuti A, Biasco L, Scaramuzza S, et al. Lentiviral hematopoietic stem cell gene therapy in patients with Wiskott-Aldrich syndrome. Science, 2013, 341(6148):1233151. doi: 10.1126/science.1233151

[60]	Cartier N, Hacein-Bey-abina S, Bartholomae C C, et al. Hematopoietic stem cell gene therapy with a lentiviral vector in X-linked adrenoleukodystrophy. Science, 2009, 326(5954):818-823. doi: 10.1126/science.1171242

[61]	Schejtman A, Vetharoy W, Choi U, et al. Preclinical optimization and safety studies of a new lentiviral gene therapy for p47phox-deficient chronic granulomatous disease. Human Gene Therapy, 2021: hum. 2020. 276.

[62]	Tran R, Myers D R, Denning G, et al. Microfluidic transduction harnesses mass transport principles to enhance gene transfer efficiency. Molecular Therapy, 2017, 25(10):2372-2382. doi: 10.1016/j.ymthe.2017.07.002

[1]	XU Ying-yong. Current Status and Challenges of Gene Therapy Products[J]. China Biotechnology, 2020, 40(12): 95-103.

[2]	CHEN Qing-yu,WANG Xian-zhong,ZHANG Jiao-jiao. Application of Gene Technology in the Treatment of Type 2 Diabetes Mellitus[J]. China Biotechnology, 2020, 40(11): 73-81.

[3]	Ya-li HAN,Guang-heng YANG,Yan-wen CHEN,Xiu-li GONG,Jing-zhi ZHANG. The Optimization of Self-deleting Lentiviral Vector Carrying Human β-globin Gene and Promoter[J]. China Biotechnology, 2018, 38(7): 50-57.

[4]	LIU Yi-xuan, BIAN Zhen, MA Hong-mei. Progress and Prospect of Cancer Gene Therapy[J]. China Biotechnology, 2016, 36(5): 106-111.

[5]	TAO Chang-li, HUANG Shu-lin. *Advances in Research on Optimization of Transgenic TCR* Pairing in TCR Gene Therapy**[J]. China Biotechnology, 2016, 36(3): 87-92.

[6]	LIU Rui-qi, WANG Wei-wei, WU Yong-yan, ZHAO Qiu-yun, WANG Yong-sheng, QING Su-zhu. Research Progress of CRISPR-Cas9 and Its Application in Gene Therapy[J]. China Biotechnology, 2016, 36(10): 72-78.

[7]	ZHU Shao-yi, GUAN Li-hong, LIN Jun-tang. CRISPR-Cas9 System and Its Applications in Disease Models[J]. China Biotechnology, 2016, 36(10): 79-85.

[8]	XUE Jin-feng, XUE Zhi-gang, CHEN Yi-yao, LI Zhuo, YIN Biao, WU Ling-qian, LIANG De-sheng. In vitro and in vivo Gene Therapy Research of CDTK Genes Drove by Enhanced Tumor-specific Promoter in Liver Cancer[J]. China Biotechnology, 2015, 35(6): 1-7.

[9]	XUE Yu-wen, LI Tie-jun, ZHOU Jia-ming, CHEN Li. The Application and Perspectives of Multi-target RNAi in the Research and Development of Gene Therapy[J]. China Biotechnology, 2015, 35(1): 75-81.

[10]	MA Bu-yun, HE Wan-wan, ZHOU Li, WANG Yi-gang. The Study on Anticancer Effect of Targeting Gene-Virus ZD55-XAF1 in Liver Cancer Xenograft of Mice and Its Safety[J]. China Biotechnology, 2014, 34(1): 15-20.

[11]	FAN Fu, CHEN Jian-guo, REN Hong-wei. Development of Gene Therapy for Parkinson’s Disease And Alzheimer’s Disease[J]. China Biotechnology, 2013, 33(4): 129-135.

[12]	LIU Si-ye, XIA Hai-bin. A New Targeted Gene Editing Technology Mediated by CRISPR-Cas System[J]. China Biotechnology, 2013, 33(10): 117-123.

[13]	CHEN Feng, YANG Yi-shu, ZENG Yi. Current Development on RNA-based Anti-HIV-1 Gene Therapy[J]. China Biotechnology, 2012, 32(6): 93-97.

[14]	DIAO Yong, QIU Fei, XIAO Wei-dong. Package Capacity Limit of Recombinant Adeno-associated Virus Vector[J]. China Biotechnology, 2012, 32(01): 97-102.

[15]	SUN Qiang-ming, PAN Yue, ZHAO Yu-jiao, CHEN Jun-ying, SHI Hai-jing, MA Shao-hui. Construction and Identification of a Lentiviral Vector Expressing Semaphorin 4D[J]. China Biotechnology, 2011, 31(7): 1-7.

Viewed

Full text

Abstract

Cited

Shared

Discussed