In vivo gene delivery and expression by bacteriophage lambda vectors

Lankes, Heather A.; Zanghi, Christine N.; Santos, Kathlyn; Capella, Cristina; Duke, C.M.P.; Dewhurst, Stephen

doi:10.1111/j.1365-2672.2006.03182.x

Cited by 58 publications

(50 citation statements)

References 48 publications

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“…Lambda bacteriophages are used in gene transfer and vaccine delivery because of their capacity to transduce mammalian cells in vivo 10 . Tyler and collaborators recently showed that prophage induction is required for renal disease and lethality in the EHEC mouse model, suggesting that free bacteriophages encoding Stx may play a direct role in the disease 3 .…”

Section: Discussionmentioning

confidence: 99%

Role of bacteriophages in STEC infections: new implications for the design of prophylactic and treatment approaches

et al. 2014

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Shiga toxin (Stx) is considered the main virulence factor in Shiga toxin-producing Escherichia coli (STEC) infections. Previously we reported the expression of biologically active Stx by eukaryotic cells in vitro and in vivo following transfection with plasmids encoding Stx under control of the native bacterial promoter. Since stx genes are present in the genome of lysogenic bacteriophages, here we evaluated the relevance of bacteriophages during STEC infection. We used the non-pathogenic E. coli K12 strain carrying a lysogenic 933W mutant bacteriophage in which the stx operon was replaced by a gene encoding the green fluorescent protein (GFP). Tracking GFP expression using an In Vivo Imaging System (IVIS), we detected fluorescence in liver, kidney, and intestine of mice infected with the recombinant E. coli strain after treatment with ciprofloxacin, which induces the lytic replication and release of bacteriophages.In addition, we showed that chitosan, a linear polysaccharide composed of D-glucosamine residues and with a number of commercial and biomedical uses, had strong anti-bacteriophage effects, as demonstrated in vitro and in vivo. These findings bring promising perspectives for the prevention and treatment of hemolytic uremic syndrome (HUS) cases.

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Section: Discussionmentioning

confidence: 99%

Role of bacteriophages in STEC infections: new implications for the design of prophylactic and treatment approaches

et al. 2014

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“…Bacteriophages are also stable, compatible with simple storage and formulation methods, inexpensive to produce, and suitable for large-scale production and have an established safety record for use in humans (11). Therefore, if successful, this expression system could potentially lead to development of an easily implementable and economical strategy for the prevention of HIV infection across mucosal membranes.…”

Section: Discussionmentioning

confidence: 99%

Plasmid Transduction Using Bacteriophage Φadh for Expression of CC Chemokines byLactobacillus gasseriADH

Damelin¹,

Mavri-Damelin

Klaenhammer

et al. 2010

Appl Environ Microbiol

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Vaginal mucosal microfloras are typically dominated by Gram-positive Lactobacillus species, and colonization of vaginal mucosa by exogenous microbicide-secreting Lactobacillus strains has been proposed as a means of enhancing this natural mucosal barrier against human immunodeficiency virus (HIV) infection. We asked whether an alternative strategy could be utilized whereby anti-HIV molecules are expressed within the cervicovaginal milieu by endogenous vaginal Lactobacillus populations which have been engineered in situ via transduction. In this study, we therefore investigated the feasibility of utilizing transduction for the expression of two HIV coreceptor antagonists, the CC chemokines CCL5 and CCL3, in a predominant vaginal Lactobacillus species, Lactobacillus gasseri. Modifying a previously established transduction model, which utilizes L. gasseri ADH and its prophage ⌽adh, we show that mitomycin C induction of L. gasseri ADH transformants containing pGK12-based plasmids with CCL5 and CCL3 expression and secretion cassettes (under the control of promoters P6 and P59, respectively) and a 232-bp ⌽adh cos site fragment results in the production of transducing particles which contain 8 to 9 copies of concatemeric plasmid DNA. High-frequency transduction for these particles (almost 6 orders of magnitude greater than that for pGK12 alone) was observed, and transductants were found to contain recircularized expression plasmids upon subsequent culture. Importantly, transductants produced CC chemokines at levels comparable to those produced by electroporation-derived transformants. Our findings therefore lend support to the potential use of transduction in vaginal Lactobacillus species as a novel strategy for the prevention of HIV infection across mucosal membranes.

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“…The results indicate that even unmodified nontargeted -phage particles can mediate in vivo gene delivery, possibly due to their uptake by AP cells. Addressing the mechanism of phage-mediated gene transfer, and to test whether phagocytosis was required for this process, the findings by Lankes et al [21] showed phagocytosis to be responsible for a portion but not the majority of phage-mediated gene transfer. It is more likely that nonphagocytic mechanisms contribute to the uptake of phage particles and expression of phageencoded proteins.…”

Section: Discussionmentioning

confidence: 99%

Protection of Mice by a λ-Based Therapeutic Vaccine against Cancer Associated with Human Papillomavirus Type 16

Ghaemi

Soleimanjahi²,

Gill

et al. 2010

Intervirology

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Objective: Human papillomavirus (HPV) oncoproteins (i.e. E6 and E7) are constitutively expressed in cervical cancer cells. The proteins are ideal targets to be used for developing therapeutic vaccines against existing HPV-associated carcinomas. To date, whole bacteriophage (‘phage’)-λ particles, rather than purified ‘naked’ DNA, have been described as highly efficient delivery vehicles for a DNA vaccine. Methods: In this study, a safe and efficient λ-based therapeutic cancer vaccine, recombinant λ-ZAP E7 phage, was developed by inserting a HPV16 E7 gene into the Lambda ZAP® cytomegalovirus vector. λ-ZAP E7 phages were employed to immunize mice against the E7-expressing murine tumor cell line (TC-1), which is used as a tumor model in an H-2b murine system. Results: The tumor-bearing mice indicated a significant inhibition of tumor growth after 3 injections of 2 × 10¹² particles of recombinant phages. Released lactate dehydrogenase, interferon-γ and granzyme B from spleen cells and lymphocyte proliferation of spleen cells, which all demonstrate the enhancement of cell-mediated immunity, suggested the phages could be a potent gene delivery system in animal models. Conclusion: Our results suggest the recombinant phages can be used as effective biological tools for inducing E7-specific protective immune responses. Hence, the study introduces a possible therapeutic strategy against cervical cancer and other HPV-related neoplasia.

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In vivo gene delivery and expression by bacteriophage lambda vectors

Cited by 58 publications

References 48 publications

Role of bacteriophages in STEC infections: new implications for the design of prophylactic and treatment approaches

Role of bacteriophages in STEC infections: new implications for the design of prophylactic and treatment approaches

Plasmid Transduction Using Bacteriophage Φadh for Expression of CC Chemokines byLactobacillus gasseriADH

Protection of Mice by a λ-Based Therapeutic Vaccine against Cancer Associated with Human Papillomavirus Type 16

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