Gene therapy using bacterial vectors

Celec, Peter; Gardlík, Roman

doi:10.2741/4473

Cited by 17 publications

(6 citation statements)

References 79 publications

(87 reference statements)

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“…The technique is also known as bactofection, in which the live bacteria are directly used to transfer the DNA to the target cells, tissues, or organs [ 18 ]. Bactofection has been widely used in the field of drug development research [ 19 ], such as cancer treatment [ 20 ], infections [ 21 ], inflammation diseases and other metabolic diseases [ 22 , 23 ]. As a DNA vaccine carrier, both native [ 24 ] or recombinant bacteria can be used.…”

Section: Introductionmentioning

confidence: 99%

Live Bacterial Vectors—A Promising DNA Vaccine Delivery System

Yurina

2018

Medical Sciences

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Vaccination is one of the most successful immunology applications that has considerably improved human health. The DNA vaccine is a new vaccine being developed since the early 1990s. Although the DNA vaccine is promising, no human DNA vaccine has been approved to date. The main problem facing DNA vaccine efficacy is the lack of a DNA vaccine delivery system. Several studies explored this limitation. One of the best DNA vaccine delivery systems uses a live bacterial vector as the carrier. The live bacterial vector induces a robust immune response due to its natural characteristics that are recognized by the immune system. Moreover, the route of administration used by the live bacterial vector is through the mucosal route that beneficially induces both mucosal and systemic immune responses. The mucosal route is not invasive, making the vaccine easy to administer, increasing the patient’s acceptance. Lactic acid bacterium is one of the most promising bacteria used as a live bacterial vector. However, some other attenuated pathogenic bacteria, such as Salmonella spp. and Shigella spp., have been used as DNA vaccine carriers. Numerous studies showed that live bacterial vectors are a promising candidate to deliver DNA vaccines.

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Section: Introductionmentioning

confidence: 99%

Live Bacterial Vectors—A Promising DNA Vaccine Delivery System

Yurina

2018

Medical Sciences

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“…Gene therapy strategies combine methods to introduce DNA into specific human cell types and to promote DNA integration in the human genome for stable expression. Bacteria have previously been used as vectors for DNA delivery into mammalian cells; the process, known as bactofection, is based on the engulfment of bacteria by an eukaryotic cell, which causes bacterial lysis and DNA release ( Celec and Gardlik, 2017 ). We have previously shown that DNA of any origin and length can be introduced into specific human cell types using B. henselae as a delivery agent ( Fernandez-Gonzalez et al, 2011 ).…”

Section: Introductionmentioning

confidence: 99%

DNA Delivery and Genomic Integration into Mammalian Target Cells through Type IV A and B Secretion Systems of Human Pathogens

et al. 2017

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We explore the potential of bacterial secretion systems as tools for genomic modification of human cells. We previously showed that foreign DNA can be introduced into human cells through the Type IV A secretion system of the human pathogen Bartonella henselae. Moreover, the DNA is delivered covalently attached to the conjugative relaxase TrwC, which promotes its integration into the recipient genome. In this work, we report that this tool can be adapted to other target cells by using different relaxases and secretion systems. The promiscuous relaxase MobA from plasmid RSF1010 can be used to deliver DNA into human cells with higher efficiency than TrwC. MobA also promotes DNA integration, albeit at lower rates than TrwC. Notably, we report that DNA transfer to human cells can also take place through the Type IV secretion system of two intracellular human pathogens, Legionella pneumophila and Coxiella burnetii, which code for a distantly related Dot/Icm Type IV B secretion system. This suggests that DNA transfer could be an intrinsic ability of this family of secretion systems, expanding the range of target human cells. Further analysis of the DNA transfer process showed that recruitment of MobA by Dot/Icm was dependent on the IcmSW chaperone, which may explain the higher DNA transfer rates obtained. Finally, we observed that the presence of MobA negatively affected the intracellular replication of C. burnetii, suggesting an interference with Dot/Icm translocation of virulence factors.

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“…For oral administration of DNA, non-pathogenic ( L. lactis [ 221 ] or attenuated ( S. thyphimurium [ 222 ] and L. monocytogenes [ 223 ]) bacterial strains are often used as vectors, termed bactofection [ 224 ]. In the intestine, these bacteria may be phagocytosed directly by mucosal DC/macrophages spreading extensions into the gut lumen or after M cell-mediated transcytosis at the Peyer’s patches [ 225 ].…”

Section: Route Of Vaccinationmentioning

confidence: 99%

DNA Vaccines—How Far From Clinical Use?

Hobernik

Bros

2018

IJMS

374

332

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Two decades ago successful transfection of antigen presenting cells (APC) in vivo was demonstrated which resulted in the induction of primary adaptive immune responses. Due to the good biocompatibility of plasmid DNA, their cost-efficient production and long shelf life, many researchers aimed to develop DNA vaccine-based immunotherapeutic strategies for treatment of infections and cancer, but also autoimmune diseases and allergies. This review aims to summarize our current knowledge on the course of action of DNA vaccines, and which factors are responsible for the poor immunogenicity in human so far. Important optimization steps that improve DNA transfection efficiency comprise the introduction of DNA-complexing nano-carriers aimed to prevent extracellular DNA degradation, enabling APC targeting, and enhanced endo/lysosomal escape of DNA. Attachment of virus-derived nuclear localization sequences facilitates nuclear entry of DNA. Improvements in DNA vaccine design include the use of APC-specific promotors for transcriptional targeting, the arrangement of multiple antigen sequences, the co-delivery of molecular adjuvants to prevent tolerance induction, and strategies to circumvent potential inhibitory effects of the vector backbone. Successful clinical use of DNA vaccines may require combined employment of all of these parameters, and combination treatment with additional drugs.

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Gene therapy using bacterial vectors

Cited by 17 publications

References 79 publications

Live Bacterial Vectors—A Promising DNA Vaccine Delivery System

Live Bacterial Vectors—A Promising DNA Vaccine Delivery System

DNA Delivery and Genomic Integration into Mammalian Target Cells through Type IV A and B Secretion Systems of Human Pathogens

DNA Vaccines—How Far From Clinical Use?

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