Targeting Lentiviral Vectors to Antigen-Specific Immunoglobulins

Ziegler, Leslie; Yang, Lili; Joo, Kye-Il; Yang, Haiguang; Baltimore, David; Wang, Pin

doi:10.1089/hgt.2007.149

Cited by 17 publications

(24 citation statements)

References 36 publications

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“…3B, lower panel). This apparently low CD20 expression level can be partially attributed to the insensitivity of the anti-CD20 staining antibody, which was documented in a previous study (Ziegler et al, 2008). As expected from the previous inverse fusion study, the producing cells could co-express both CD4 and a co-receptor (CCR5 or CXCR4) on their surfaces (Fig.…”

Section: Resultssupporting

confidence: 59%

“…The working mechanism of this suicide gene approach is that the otherwise non-toxic prodrug ganciclovir (GCV), when supplied to the target cells, is transformed into a toxic metabolite by the HSV1-TK expressed in the cells to mediate specific killing (Blumenthal et al, 2007). The HSV1-TK-encoding lentiviral backbone plasmid FUWSR39tk, constructed in our laboratory and reported previously (Ziegler et al, 2008), was used in this experiment. The mixed population of Env-expressing Jurkat cells described above was challenged with the FUWSR39tk/CD4+SGN vector three times, followed by further culture in media with or without the supplement of the prodrug GCV for an additional seven days.…”

Section: Resultsmentioning

confidence: 99%

“…The HIV-1-based lentiviral vector FUGW was reported by Dr. David Baltimore’s Laboratory (Lois et al, 2002) and used in this study. The suicide gene, the mutant of Herpes Simplex Virus-1 thymidine kinase SR39Tk, was amplified from a reported construct (Black et al, 2001) and cloned downstream of the human ubiquitin-C promoter in the lentiviral vector plasmid FUW (Ziegler et al, 2008). The construct was referred to as FUWSR39TK.…”

Section: Methodsmentioning

confidence: 99%

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Engineered lentiviral vectors pseudotyped with a CD4 receptor and a fusogenic protein can target cells expressing HIV-1 envelope proteins

et al. 2011

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Lentiviral vectors (LVs) derived from human immunodeficiency virus type 1 (HIV-1) are promising vehicles for gene delivery because they not only efficiently transduce both dividing and non-dividing cells, but also maintain long-term transgene expression. Development of an LV system capable of transducing cells in a cell type-specific manner can be beneficial for certain applications that rely on targeted gene delivery. Previously it was shown that an inverse fusion strategy that incorporated an HIV-1 receptor (CD4) and its co-receptor (CXCR4 or CCR5) onto vector surfaces could confer to LVs the ability to selectively deliver genes to HIV-1 envelope-expressing cells. To build upon this work, we aim to improve its relatively low transduction efficiency and circumvent its inability to target multiple tropisms of HIV-1 by a single vector. We investigated a method to create LVs co-enveloped with the HIV-1 cellular receptor CD4 and a fusogenic protein derived from the Sindbis virus glycoprotein and tested its efficiency to selectively deliver genes into cells expressing HIV-1 envelope proteins. The engineered LV system yields a higher level of transduction efficiency and a broader tropism towards cells displaying the HIV-1 envelope protein (Env) than the previously developed system. Furthermore, we demonstrated in vitro that this engineered LV can preferentially deliver suicide gene therapy to HIV-1 envelope-expressing cells. We conclude that it is potentially feasible to target LVs towards HIV-1-infected cells by functional co-incorporation of the CD4 and fusogenic proteins, and provide preliminary evidence for further investigation on a potential alternative treatment for eradicating HIV-1-infected cells that produce drug-resistant viruses after highly active antiretroviral therapy (HAART).

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Section: Resultssupporting

confidence: 59%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Engineered lentiviral vectors pseudotyped with a CD4 receptor and a fusogenic protein can target cells expressing HIV-1 envelope proteins

et al. 2011

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“…However, primary resting B cells, like other G 0 -arrested quiescent cells of the hematopoietic system, require cytokine- or CD40-mediated stimulation to the G 1 phase to become efficiently transduced by conventional lentiviral or retroviral vectors, which is not desirable for in vivo applications or for tolerogenic studies 16, 17, 18. Measles virus (MV) hemagglutinin (H) and fusion (F) envelope protein pseudotyped LVs (MV-LV) have recently been shown to efficiently enter and integrate into non-activated B and T lymphocytes 19 .…”

Section: Introductionmentioning

confidence: 99%

Immune Modulatory Cell Therapy for Hemophilia B Based on CD20-Targeted Lentiviral Gene Transfer to Primary B Cells

Wang

Herzog

Byrne

et al. 2017

Molecular Therapy - Methods & Clinical Development

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Gene-modified B cells expressing immunoglobulin G (IgG) fusion proteins have been shown to induce tolerance in several autoimmune and other disease models. However, lack of a vector suitable for gene transfer to human B cells has been an obstacle for translation of this approach. To overcome this hurdle, we developed an IgG-human factor IX (hFIX) lentiviral fusion construct that was targeted to specifically transduce cells expressing human CD20 (hCD20). Receptor-specific retargeting by mutating envelope glycoproteins of measles virus (MV)-lentiviral vector (LV) and addition of a single-chain variable fragment specific for hCD20 resulted in gene delivery into primary human and transgenic hCD20 mouse B cells with high specificity. Notably, this protocol neither required nor induced activation of the B cells, as confirmed by minimal activation of inflammatory cytokines. Using this strategy, we were able to demonstrate induction of humoral tolerance, resulting in suppression of antibody formation against hFIX in a mouse model of hemophilia B (HB). In conclusion, transduction of receptor-specific retargeted LV into resting B cells is a promising method to develop B cell therapies for antigen-specific tolerance induction in human disease.

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“…Several such approaches have been developed and demonstrated in cell culture (for review, see refs. 6 and 7), and more recently, to target B lymphocytes in the blood (8) or s.c.-injected tumor cells in vivo (9). However, we are not aware of any successful demonstrations after injections into a complex solid tissue, such as the brain, in vivo.…”

mentioning

confidence: 99%

Selective viral vector transduction of ErbB4 expressing cortical interneurons in vivo with a viral receptor–ligand bridge protein

Choi¹,

Young

Callaway³

2010

Proc. Natl. Acad. Sci. U.S.A.

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Both treatment of disease and basic studies of complex tissues can benefit from directing viral vector infection to specific cell types. We have used a unique cell targeting method to direct viral vector transduction to cerebral cortical neurons expressing the neuregulin (NRG) receptor ErbB4; both NRG and ErbB4 have been implicated in schizophrenia, and ErbB4 expression in cerebral cortex is known to be restricted to inhibitory neurons. We find that a bridge protein composed of the avian viral receptor TVB fused to NRG, along with EnvB-psuedotyped virus, is able to direct infection selectively to ErbB4-expressing inhibitory cortical neurons in vivo. Interestingly, although ErbB4 is expressed in a broad range of cortical inhibitory cell types, NRG-dependent infection is restricted to a more selective subset of inhibitory cell types. These results demonstrate a tool that can be used for further studies of NRG and ErbB receptors in brain circuits and demonstrate the feasibility for further development of related bridge proteins to target gene expression to other specific cell types in complex tissues.

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Targeting Lentiviral Vectors to Antigen-Specific Immunoglobulins

Cited by 17 publications

References 36 publications

Engineered lentiviral vectors pseudotyped with a CD4 receptor and a fusogenic protein can target cells expressing HIV-1 envelope proteins

Engineered lentiviral vectors pseudotyped with a CD4 receptor and a fusogenic protein can target cells expressing HIV-1 envelope proteins

Immune Modulatory Cell Therapy for Hemophilia B Based on CD20-Targeted Lentiviral Gene Transfer to Primary B Cells

Selective viral vector transduction of ErbB4 expressing cortical interneurons in vivo with a viral receptor–ligand bridge protein

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