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Lysibodies

Creative Biolabs is a leading contract research organization (CRO) providing standard and customized testing services. We have extensive experience in developing "fit for purpose" experiments. Our mission is to efficiently drive client projects by providing special, customized phage research services.

Background

The emergence of multidrug-resistant bacteria has created a need for alternatives to traditional antibiotics. One important approach is the use of therapeutic antibodies, which have recently become mainstream in fields such as cancer treatment and inflammation and are now increasingly being developed to treat infectious diseases. Therapeutic antibodies and vaccines are now being actively pursued as alternative treatments for antibiotic-resistant bacterial pathogens. By establishing IgG Fc fusions of different cell wall hydrolase binding domains, scientists generated "lysibodies" specific for bacterial cell wall carbohydrate epitopes. The lysibody is a chimera between the Fc region of the human IgG antibody and the carbohydrate-binding domain derived from a cell wall hydrolase. Carbohydrates are a major component of the cell wall of Gram-positive bacteria and are promising targets for the development of therapeutic antibodies due to their abundance and high conservation.

Lysibodies

Functions

Lysibodies have all the effector functions of normal IgG antibodies, exhibit potent complement fixation and phagocytosis induction, and can protect mice from lethal attack by MRSA. The lysibody approach represents a novel and reproducible approach to generating effective immunity against conserved cell wall carbohydrates on the surface of Gram-positive bacterial pathogens, leading to their elimination. A slightly different approach has been used to produce lysibody containing binding domains from phage lysins. Unlike autolysin, most phage lysins have cell wall-binding domains located at the C-terminus of the molecule. Considering the abundance of autolysins and phage lysins found in nature, lysibodies can be produced for a range of additional Gram-positive pathogenic bacteria. Thus, lysibodies represent a broad class of anti-infective agents that address the long-standing problem of effective targeting of bacterial surface carbohydrates by antibodies.

Lysibodies protect mice from MRSA infection in kidney abscess and bacteremia models.Fig.1 Lysibodies protect mice from MRSA infection in kidney abscess and bacteremia models. (Raz, 2017)

Mode of Action

Phages produce cell wall hydrolases, called lysins, during their lytic cycle to degrade the cell wall of the infected bacterial host and release progeny phages.

Advantages

The main advantage of lysibodies over typical MAbs is the ability to bind abundant carbohydrate targets on bacterial walls that are highly conserved and therefore less likely to mutate to avoid binding. Another advantage of targeting wall carbohydrates is that they are often conserved across species, resulting in a wide range of targeted organisms. Lysibodies could offer a unique solution. By targeting highly abundant, conserved, and indispensable carbohydrate epitopes, lysibodies may yield better results than previous single-target therapeutic antibodies.

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Reference:

  1. Raz, A.; et al. Lysibodies are IgG Fc fusions with lysin binding domains targeting Staphylococcus aureus wall carbohydrates for effective phagocytosis. Proceedings of the National Academy of Sciences. 2017, 114(18): 4781-4786.
For Research Use Only. Do NOT use in humans.

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