Nuclear localization signals in phage terminal proteins provide a novel gene delivery tool in mammalian cells

Redrejo-Rodríguez, Modesto; Muñoz‐Espín, Daniel; Holguera, Isabel; Mencı́a, Mario; Salas, Margarita

doi:10.4161/cib.22829

Cited by 11 publications

(7 citation statements)

References 18 publications

(19 reference statements)

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“…Finally, it should be mentioned that Φ29 or Adenovirus replication systems have been successfully engineered for the generation ad hoc of protein-capped DNAs for diverse biotechnological purposes (36,53,54). Interestingly, since Bam35 and related tectiviruses can replicate as episomal linear plasmids in bacteria, they might be manipulated or evolved both in vitro or in vivo , as per convenience.…”

Section: Discussionmentioning

confidence: 99%

Disclosing early steps of protein-primed genome replication of the Gram-positive tectivirus Bam35

Berjón-Otero¹,

Villar²,

Salas³

et al. 2016

Nucleic Acids Res

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Protein-primed replication constitutes a generalized mechanism to initiate DNA or RNA synthesis in a number of linear genomes of viruses, linear plasmids and mobile elements. By this mechanism, a so-called terminal protein (TP) primes replication and becomes covalently linked to the genome ends. Bam35 belongs to a group of temperate tectiviruses infecting Gram-positive bacteria, predicted to replicate their genomes by a protein-primed mechanism. Here, we characterize Bam35 replication as an alternative model of protein-priming DNA replication. First, we analyze the role of the protein encoded by the ORF4 as the TP and characterize the replication mechanism of the viral genome (TP-DNA). Indeed, full-length Bam35 TP-DNA can be replicated using only the viral TP and DNA polymerase. We also show that DNA replication priming entails the TP deoxythymidylation at conserved tyrosine 194 and that this reaction is directed by the third base of the template strand. We have also identified the TP tyrosine 172 as an essential residue for the interaction with the viral DNA polymerase. Furthermore, the genetic information of the first nucleotides of the genome can be recovered by a novel single-nucleotide jumping-back mechanism. Given the similarities between genome inverted terminal repeats and the genes encoding the replication proteins, we propose that related tectivirus genomes can be replicated by a similar mechanism.

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Section: Discussionmentioning

confidence: 99%

Disclosing early steps of protein-primed genome replication of the Gram-positive tectivirus Bam35

Berjón-Otero¹,

Villar²,

Salas³

et al. 2016

Nucleic Acids Res

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“…e nuclear localization signal is a specific sequence that allows an uptake and delivery of proteins into the eukaryotic nucleus; thus, these TP-DNA molecules are a useful tool to amplify and subsequently deliver genes efficiently into the eukaryotic nucleus [69]. Meanwhile, TP is a protein used by bacteriophages to prime the DNA for replication.…”

Section: Bacteriophages Engage In Direct Hgt With Eukaryotesmentioning

confidence: 99%

Interactions between Bacteriophages and Eukaryotic Cells

Putra

Lyrawati

2020

Scientifica

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As the name implies, bacteriophage is a bacterium-specific virus. It infects and kills the bacterial host. Bacteriophages have gained attention as alternative antimicrobial entities in the science community in the western world since the alarming rise of antibiotic resistance among microbes. Although generally considered as prokaryote-specific viruses, recent studies indicate that bacteriophages can interact with eukaryotic organisms, including humans. In the current review, these interactions are divided into two categories, i.e., indirect and direct interactions, with the involvement of bacteriophages, bacteria, and eukaryotes. We discuss bacteriophage-related diseases, transcytosis of bacteriophages, bacteriophage interactions with cancer cells, collaboration of bacteriophages and eukaryotes against bacterial infections, and horizontal gene transfer between bacteriophages and eukaryotes. Such interactions are crucial for understanding and developing bacteriophages as the therapeutic agents and pharmaceutical delivery systems. With the advancement and combination of in silico, in vitro, and in vivo approaches and clinical trials, bacteriophages definitely serve as useful repertoire for biologic target-based drug development to manage many complex diseases in the future.

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“…Luckily, nuclear localization signal (NLS) can be recognized by the nuclear transport proteins and help genes arrive at the nucleus. It has been reported that NLSs exist in the terminal proteins (TPs) of many bacteriophages, such as Ф29, Nf, PRD1, Bam35, Cp-1 and YS61 (Redrejo-Rodríguez et al., 2012 ; Redrejo-Rodríguez et al., 2013 ; Redrejo-Rodríguez & Salas, 2014 ). At present, no NLSs have been found in filamentous bacteriophage.…”

Section: Identification Of Targeting Using Phage Librariesmentioning

confidence: 99%

Drug delivery vectors based on filamentous bacteriophages and phage-mimetic nanoparticles

Zhang

Sun

2017

Drug Delivery

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With the development of nanomedicine, a mass of nanocarriers have been exploited and utilized for targeted drug delivery, including liposomes, polymers, nanoparticles, viruses, and stem cells. Due to huge surface bearing capacity and flexible genetic engineering property, filamentous bacteriophage and phage-mimetic nanoparticles are attracting more and more attentions. As a rod-like bio-nanofiber without tropism to mammalian cells, filamentous phage can be easily loaded with drugs and directly delivered to the lesion location. In particular, chemical drugs can be conjugated on phage surface by chemical modification, and gene drugs can also be inserted into the genome of phage by recombinant DNA technology. Meanwhile, specific peptides/proteins displayed on the phage surface are able to conjugate with nanoparticles which will endow them specific-targeting and huge drug-loading capacity. Additionally, phage peptides/proteins can directly self-assemble into phage-mimetic nanoparticles which may be applied for self-navigating drug delivery nanovehicles. In this review, we summarize the production of phage particles, the identification of targeting peptides, and the recent applications of filamentous bacteriophages as well as their protein/peptide for targeting drug delivery in vitro and in vivo. The improvement of our understanding of filamentous bacteriophage and phage-mimetic nanoparticles will supply new tools for biotechnological approaches.

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Nuclear localization signals in phage terminal proteins provide a novel gene delivery tool in mammalian cells

Cited by 11 publications

References 18 publications

Disclosing early steps of protein-primed genome replication of the Gram-positive tectivirus Bam35

Disclosing early steps of protein-primed genome replication of the Gram-positive tectivirus Bam35

Interactions between Bacteriophages and Eukaryotic Cells

Drug delivery vectors based on filamentous bacteriophages and phage-mimetic nanoparticles

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