Lysin-deficient bacteriophages having reduced immunogenicity

Details Lysin-deficient bacteriophages having reduced immunogenicity Lysin-deficient bacteriophages having reduced immunogenicity

A - Human Necessities

01

N

A01N 63/00 (2006.01) A61K 35/76 (2006.01) C12N 7/00 (2006.01) C12Q 1/70 (2006.01)

Patent

CA 2461647

The present invention features therapeutic bacteriophage deficient in the lysin protein ("Lys minus" phage). Lys minus bacteriophage are incapable of facilitating efficient lysis of the bacterial host since the enzymatic activity of the lysin of the phage is needed for breaking down the peptidoglycan layer of the bacterial cell wall. Lys minus bacteriophage retain activity in invasion of its appropriate bacterial host, destruction of the bacterial genome, and replication, which are sufficient to inhibit bacterial growth and replication. Therefore, the therapeutic Lys minus phage stops the spread of infection by the bacterial pathogen without lysis of the bacterium. This approach is attractive as it also prevents the release of the phage progeny, thus reducing or eliminating the potential for generation of immune responses against the phage. The incapacitated bacterial pathogen is then removed by the normal defense systems such as phagocytes and macrophages.

L'invention concerne un bactériophage thérapeutique déficient en protéine lysine (phage "Lys-moins"). Les bactériophages Lys-moins sont incapables de faciliter une lyse efficace de l'hôte bactérien puisque l'activité enzymatique de la lysine du phage est requise pour casser la couche de peptidoglucane de la paroi cellulaire bactérienne. Les bactériophages Lys-moins maintiennent une activité d'invasion de leur hôte bactérien adéquat, de destruction du génome bactérien, et de replication, ce qui suffit à inhiber la croissance et la replication bactérienne. Ainsi, le phage thérapeutique Lys-moins stoppe la propagation de l'infection du pathogène bactérien sans réaliser la lyse de la bactérie. Cette approche est intéressante dans la mesure où elle permet aussi d'empêcher la libération de génome de descendance, ce qui réduit ou élimine le risque de déclencher des réponses immunes contre le phage. Le pathogène bactérien frappé d'incapacité est alors éliminé par les système de défense normaux notamment par le biais de phagocytes et de macrophages.

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