CRISPR-Cas nucleases are able to be targeted easily to specific sites in the genome, using a guide RNA designed specifically for that purpose. This is advantageous over traditional antibiotics, as it is highly specific, identifying only the one species causing the infection while leaving commensal bacteria unaffected. ‘Traditional antibiotics’, those used clinically today, typically have a broad spectrum of activity, killing a wide range of bacteria. This can result in many side effects (GI disturbance, Chron’s disease, …), especially with antibiotics used in hospitals under closer clinical supervision, due to the indiscriminate killing activity they posses. This has resulted in concerns around antibiotic resistance, which is likely to become a larger issue in the coming years - although this is largely due to overuse and abuse in agricultural settings (where antibiotics can be used as growth enhancers and prophylactics).
Using CRISPR-Cas as an antimicrobial, delivered by a phagemid, would allow highly specific targeting of antimicrobial activity. This specificity reduces the side effects a patient would experience, as well as reducing the possibility of resistance arising.
However, there are some disadvantages to treating with CRISPR-Cas antimicrobials. Bacteria can become resistant to phage attack, through the same mechanisms that CRISPR employs. This could be overcome by changing the region the antimicrobial identifies in the bacterial chromosome, however the current regulatory environment for drugs would make this prohibitively expensive and complicated. The specificity of the phagemid, which has properties of M13 phage, is high, with each bacterial species needing modifications. This increases the complexity over current antimicrobials, and again is impeded by current drug safety regulations. The current best route is to develop new small molecule antimicrobials, and reduce excessive use of existing antimicrobials to preserve the efficacy.