HSV Recombinant Vectors for Gene Therapy

Manservigi, Roberto; Argnani, Rafaela; Marconi, Peggy

doi:10.2174/1874357901004010123

Cited by 56 publications

(74 citation statements)

References 342 publications

(186 reference statements)

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“…Oncolytic human herpes simplex viruses (HSV) have been genetically engineered to limit neurovirulence and the establishment of latency and reactivation and to replicate exclusively in cells with deficient apoptotic mechanisms (i.e., cancer cells) (5,6,37). These genetic changes are fundamental to the safety and efficacy of oncolytic herpesviruses but often result in rapid clearance of the virus by the host immune response, thus limiting its therapeutic potential.…”

mentioning

confidence: 99%

Oncolytic Herpes Simplex Virus 1 Encoding 15-Prostaglandin Dehydrogenase Mitigates Immune Suppression and Reduces Ectopic Primary and Metastatic Breast Cancer in Mice

Walker¹,

Sehgal

Kousoulas³

2011

J Virol

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Oncolytic human herpes simplex viruses (HSV) have been genetically engineered to limit neurovirulence and the establishment of latency and reactivation and to replicate exclusively in cells with deficient apoptotic mechanisms (i.e., cancer cells) (5, 6, 37). These genetic changes are fundamental to the safety and efficacy of oncolytic herpesviruses but often result in rapid clearance of the virus by the host immune response, thus limiting its therapeutic potential. It is precisely the antiviral immune response, however, that is thought to help overcome tumor-induced immune suppression, allowing for antitumor immunity to develop. In this regard, HSV-1 infections within tumors may function as in situ vaccines, providing the necessary inflammatory signals that engage innate and adaptive immune responses to tumor antigens. Thus, oncolytic HSV-1 may be effective both directly as a cancer killing agent and indirectly as an immunological enhancer, or in situ cancer vaccine (13,49). Previously, we reported that the novel fusogenic oncolytic herpesvirus OncSyn (OS) was effective at treating primary solid breast tumors in mice (25,26). Moreover, treatment of primary 4T1 tumors in syngeneic BALB/c mice with OS led to a substantial reduction in the formation of metastatic foci within multiple organs and in some cases eliminated lung metastasis, suggesting the development of effective antitumor immunity (43).The HSV-1 vhs gene product encoded by the UL41 open reading frame (ORF) has multiple functions that are known to suppress antiviral immune responses. (i) vhs is an RNase that degrades viral and cellular mRNAs, limiting host and viral antigen production (3,32,33,45,48,51,56,59,61,65,75). (ii) UL41 (vhs) with ICP47 is known to inhibit major histocompatibility complex I (MHC-I) antigen presentation (59), while vhs alone has also been implicated in the reduction of MHC-II expression (69). (iii) vhs has been reported to suppress production of cytokines and chemokines and inactivate dendritic cells (7,59). In agreement with these reports, deletion of the vhs gene prevented HSV-1-mediated inactivation of antigen presentation by dendritic cells (DC) (54) and improved the immunogenicity of a candidate replication-defective HSV-1 vaccine strain (16,55). Furthermore, deletion of the vhs gene causes substantial reduction in neurovirulence (48, 60, 64).

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mentioning

confidence: 99%

Oncolytic Herpes Simplex Virus 1 Encoding 15-Prostaglandin Dehydrogenase Mitigates Immune Suppression and Reduces Ectopic Primary and Metastatic Breast Cancer in Mice

Walker¹,

Sehgal

Kousoulas³

2011

J Virol

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“…The virus enters cells by fusion triggered by binding of viral glycoprotein gB and gD to the heparin sulfate moiety of the cell surface protein. [68] DNA enters the cell and circularizes.…”

Section: Herpes Simplex Viralmentioning

confidence: 99%

“…[68] A few of the immediate early protein genes were removed to generate viral vectors unable to replicate except in a complementing cell line. Because of its large genome size, the recombinant HSV vectors should be capable of containing an inserted gene up to 30 kb.…”

Section: Herpes Simplex Viralmentioning

confidence: 99%

Advances in Gene Delivery Systems

et al. 2011

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The transfer of genes into cells, both in vitro and in vivo, is critical for studying gene function and conducting gene therapy. Methods that utilize viral and nonviral vectors, as well as physical approaches, have been explored. Viral vector-mediated gene transfer employs replication-deficient viruses such as retro-virus, adenovirus, adeno-associated virus and herpes simplex virus. A major advantage of viral vectors is their high gene delivery efficiency. The nonviral vectors developed so far include cationic liposomes, cationic polymers, synthetic peptides and naturally occurring compounds. These nonviral vectors appear to be highly effective in gene delivery to cultured cells in vitro but are significantly less effective in vivo. Physical methods utilize mechanical pressure, electric shock or hydrodynamic force to transiently permeate the cell membrane to transfer DNA into target cells. They are simpler than viral-and nonviral-based systems and highly effective for localized gene delivery. The past decade has seen significant efforts to establish the most desirable method for safe, effective and target-specific gene delivery, and good progress has been made. The objectives of this review are to (i) explain the rationale for the design of viral, nonviral and physical methods for gene delivery; (ii) provide a summary on recent advances in gene transfer technology; (iii) discuss advantages and disadvantages of each of the most commonly used gene delivery methods; and (iv) provide future perspectives.

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“…In addition, preclinical studies on models of neurological disease, such as glioma, peripheral neuropathy, chronic pain and neurodegeneration, show encouraging results (Jenkins & Turner, 1996;de Silva & Bowers, 2009;Glorioso & Fink, 2009;Manservigi et al, 2010;Fraefel et al, 2011;Goins et al, 2011). …”

Section: Herpes Simplex Virusmentioning

confidence: 99%

Viral Vectors in Neurobiology: Therapeutic and Research Applications

Coura¹

2012

Molecular Virology

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HSV Recombinant Vectors for Gene Therapy

Cited by 56 publications

References 342 publications

Oncolytic Herpes Simplex Virus 1 Encoding 15-Prostaglandin Dehydrogenase Mitigates Immune Suppression and Reduces Ectopic Primary and Metastatic Breast Cancer in Mice

Oncolytic Herpes Simplex Virus 1 Encoding 15-Prostaglandin Dehydrogenase Mitigates Immune Suppression and Reduces Ectopic Primary and Metastatic Breast Cancer in Mice

Advances in Gene Delivery Systems

Viral Vectors in Neurobiology: Therapeutic and Research Applications

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