CRISPR-CAS ANTIMICROBIAL INTERVENTIONS TO COUNTERACT RESISTANCE GENE TRANSMISSION: A SYSTEMATIC REVIEW OF CURRENT PROGRESS AND DELIVERY METHODOLOGIE
Keywords:
CRISPR-Cas systems, Antimicrobial agents, Drug resistance, Nanoparticles, ESKAPE pathogensAbstract
The spread of resistance genes through mobile genetic elements within ESKAPE pathogens has grown as fast as AMR costs are estimated to reach (100 trillion dollar by 2050) .The clinical emergency has changed to horizontal dissemination, which is primarily driven by conjugative plasmids, integrative conjugative and prophages. Over the last ten years, programmable CRISPR-Cas antimicrobials have become an effective counter measure to this landscape. Since the Bikard paradigm of Cas9-loaded temperate staphylophages in 2014, the field has expanded to a portfolio of platforms, one of which, LBP-EC01, has been in human trials. The current review unites the evidence of phage, conjugative plasmid, and nanoparticle delivery format, synthesizes clinical milestones, and critically analyzes the manufacturing, economic, and anti-CRISPR biological barriers that continue to limit widespread translation. This is a descriptive-analytical synthesis since the evidence at hand is too heterogeneous to be statistically valid in the sense of endorsing statistically valid meta-analytic pooling.
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