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The preclinical and clinical progress of bacteriophages and their lytic enzymes : the parts are easier than the whole

(2019) VIRUSES-BASEL. 11(2).
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Abstract
The therapeutic potential of phages has been considered since their first identification more than a century ago. The evident concept of using a natural predator to treat bacterial infections has, however, since then been challenged considerably. Initially, the vast success of antibiotics almost eliminated the study of phages for therapy. Upon the renaissance of phage therapy research, the most provocative and unique properties of phages such as high specificity, self-replication and co-evolution prohibited a rapid preclinical and clinical development. On the one hand, the typical trajectory followed by small molecule antibiotics could not be simply translated into the preclinical analysis of phages, exemplified by the need for complex broad spectrum or personalized phage cocktails of high purity and the more complex pharmacokinetics. On the other hand, there was no fitting regulatory framework to deal with flexible and sustainable phage therapy approaches, including the setup and approval of adequate clinical trials. While significant advances are incrementally made to eliminate these hurdles, phage-inspired antibacterials have progressed in the slipstream of phage therapy, benefiting from the lack of hurdles that are typically associated with phage therapy. Most advanced are phage lytic enzymes that kill bacteria through peptidoglycan degradation and osmotic lysis. Both phages and their lytic enzymes are now widely considered as safe and have now progressed to clinical phase II to show clinical efficacy as pharmaceutical. Yet, more initiatives are needed to fill the clinical pipeline to beat the typical attrition rates of clinical evaluation and to come to a true evaluation of phages and phage lytic enzymes in the clinic.
Keywords
:phage, lytic enzyme, endolysin, antibacterial, antibiotic, preclinical analysis, clinical trial KeyWords Plus:PHAGE THERAPY, ESCHERICHIA-COLI, PSEUDOMONAS-AERUGINOSA, KLEBSIELLA-PNEUMONIAE, T2 PHAGE, SEQUENCE, ANTIBACTERIAL, LYSIS, PURIFICATION, ENDOLYSINS

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Citation

Please use this url to cite or link to this publication:

MLA
Abdelkader, Karim Abdelkader Soufi et al. “The Preclinical and Clinical Progress of Bacteriophages and Their Lytic Enzymes : the Parts Are Easier Than the Whole.” Ed. Yves Briers. VIRUSES-BASEL 11.2 (2019): n. pag. Print.
APA
Abdelkader, K. A. S., Gerstmans, H., Saafan, A., Dishisha, T., & Briers, Y. (2019). The preclinical and clinical progress of bacteriophages and their lytic enzymes : the parts are easier than the whole. (Y. Briers, Ed.)VIRUSES-BASEL, 11(2).
Chicago author-date
Abdelkader, Karim Abdelkader Soufi, Hans Gerstmans, Amal Saafan, Tarek Dishisha, and Yves Briers. 2019. “The Preclinical and Clinical Progress of Bacteriophages and Their Lytic Enzymes : the Parts Are Easier Than the Whole.” Ed. Yves Briers. Viruses-basel 11 (2).
Chicago author-date (all authors)
Abdelkader, Karim Abdelkader Soufi, Hans Gerstmans, Amal Saafan, Tarek Dishisha, and Yves Briers. 2019. “The Preclinical and Clinical Progress of Bacteriophages and Their Lytic Enzymes : the Parts Are Easier Than the Whole.” Ed. Yves Briers. Viruses-basel 11 (2).
Vancouver
1.
Abdelkader KAS, Gerstmans H, Saafan A, Dishisha T, Briers Y. The preclinical and clinical progress of bacteriophages and their lytic enzymes : the parts are easier than the whole. Briers Y, editor. VIRUSES-BASEL. 2019;11(2).
IEEE
[1]
K. A. S. Abdelkader, H. Gerstmans, A. Saafan, T. Dishisha, and Y. Briers, “The preclinical and clinical progress of bacteriophages and their lytic enzymes : the parts are easier than the whole,” VIRUSES-BASEL, vol. 11, no. 2, 2019.
@article{8608974,
  abstract     = {The therapeutic potential of phages has been considered since their first identification more than a century ago. The evident concept of using a natural predator to treat bacterial infections has, however, since then been challenged considerably. Initially, the vast success of antibiotics almost eliminated the study of phages for therapy. Upon the renaissance of phage therapy research, the most provocative and unique properties of phages such as high specificity, self-replication and co-evolution prohibited a rapid preclinical and clinical development. On the one hand, the typical trajectory followed by small molecule antibiotics could not be simply translated into the preclinical analysis of phages, exemplified by the need for complex broad spectrum or personalized phage cocktails of high purity and the more complex pharmacokinetics. On the other hand, there was no fitting regulatory framework to deal with flexible and sustainable phage therapy approaches, including the setup and approval of adequate clinical trials. While significant advances are incrementally made to eliminate these hurdles, phage-inspired antibacterials have progressed in the slipstream of phage therapy, benefiting from the lack of hurdles that are typically associated with phage therapy. Most advanced are phage lytic enzymes that kill bacteria through peptidoglycan degradation and osmotic lysis. Both phages and their lytic enzymes are now widely considered as safe and have now progressed to clinical phase II to show clinical efficacy as pharmaceutical. Yet, more initiatives are needed to fill the clinical pipeline to beat the typical attrition rates of clinical evaluation and to come to a true evaluation of phages and phage lytic enzymes in the clinic.},
  articleno    = {96},
  author       = {Abdelkader, Karim Abdelkader Soufi and Gerstmans, Hans and Saafan, Amal and Dishisha, Tarek and Briers, Yves},
  editor       = {Briers, Yves},
  issn         = {1999-4915},
  journal      = {VIRUSES-BASEL},
  keywords     = {:phage,lytic enzyme,endolysin,antibacterial,antibiotic,preclinical analysis,clinical trial   KeyWords Plus:PHAGE THERAPY,ESCHERICHIA-COLI,PSEUDOMONAS-AERUGINOSA,KLEBSIELLA-PNEUMONIAE,T2 PHAGE,SEQUENCE,ANTIBACTERIAL,LYSIS,PURIFICATION,ENDOLYSINS},
  language     = {eng},
  number       = {2},
  pages        = {16},
  title        = {The preclinical and clinical progress of bacteriophages and their lytic enzymes : the parts are easier than the whole},
  url          = {http://dx.doi.org/10.3390/v11020096},
  volume       = {11},
  year         = {2019},
}

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