Drug Development Service for CD59 (MIRL)

Complement is an important defense line of our immune system. With decades of experience, Creative Biolabs has successfully developed versatile drug discovery platforms, from which, we can provide our worldwide clients with the most diverse portfolio of standard or custom therapeutic antibodies development services. In addition, we can also offer high-quality products and valuable suggestions to promote your specific projects.

Introduction of CD59 (MIRL)

CD59 is also termed as MAC-inhibitory protein (MAC-IP), membrane inhibitor of reactive lysis (MIRL), or protectin, which in humans is encoded by the CD59 gene. As a GPI-anchored membrane protein, CD59 is widely expressed in all organs and almost all cell types, especially in cardiomyocytes and smooth muscles, where it acts as an inhibitory complement receptor to protect host cells from self-destruction by complement-mediated lysis. It is a potential target for therapeutic antibody exploration.

Structure of CD59 (MIRL)

CD59 is a membrane-bound small glycoprotein made of 77 amino acids and its molecular weight is predicted to 18-25 kDa. Unlike MCP and DAF, the structure of CD59 protein is characterized by a single cysteine-rich domain, having a hydrophobic core with three loops and a fourth helical loop, which is made of two antiparallel beta sheets. Linking each of these loops are five disulfide-bonded cysteine pairs.

Structure of the CD59 protein.

Fig.1 Structure of CD59 protein. (Hill, 2006)

Functions of CD59 (MIRL)

  1. Regulator of Complement Activation
  2. The primary function of CD59 is to inhibit the terminal step in the complement system by inhibiting MAC assembly. It can bind to C5b-8 complex to limit C9 input and prevent the formation of the polymeric C9 complex and unfolding and polymerization of the final C9 pore, thus protecting self-cells from damage caused by the activation of the terminal pathway of complement cascade.

  3. Human T Cell Immunity
  4. CD59 also plays a role in the proliferation of T cells and their ability to produce cytokines. In addition, CD59 influences the outcome of T cell response to a specific antigen. By cross-linking to lymphocytes, CD59 can stimulate the T cell, causing organization of the cytoskeleton.

CD59 regulates insulin secretion by modulating exocytotic events.

Fig.2 CD59 regulates insulin secretion by modulating exocytotic events. (Krus, 2014)

Clinical Significances

CD59a deficiency is reported to exacerbate skin autoimmune diseases, increase antichromatin autoantibody titers in murine models of Systemic Lupus Erythematosus (SLE). CD59 deficiency has also been associated with paroxysmal nocturnal hemoglobinuria (PNH), autoimmune-hemolytic anemia (AIHA), rheumatoid arthritis (RA), multiple sclerosis (MS), and Sjogren syndrome (SS).

As an important target for therapeutic antibody exploration and clinical trial, CD59 has become the global research hotspot, due to the importance in the regulation of complement activation. With advanced technologies and long-term scientific expertise, Creative Biolabs has successfully developed a series of innovative and effective therapeutic antibodies for related diseases. Now, we are proud to offer a full range of formulation development services for complement drug discovery.

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References
1. Hill, A.; et al. Protection of erythrocytes from human complement-mediated lysis by membrane-targeted recombinant soluble CD59: a new approach to PNH therapy. Blood. 2006, 107(5): 2131-2137.
2. Krus, U.; et al. The complement inhibitor CD59 regulates insulin secretion by modulating exocytotic events. Cell metabolism. 2014, 19(5): 883-890.

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Questions & Answer

A: One key challenge is achieving specificity, as modulating the complement system can have wide-ranging effects on the immune response. Ensuring that a drug specifically targets CD59 without interfering with other complement regulatory proteins is crucial. Additionally, designing drugs that can effectively cross cell membranes to reach intracellular CD59 and modulate its function is another hurdle. Furthermore, understanding the complex interactions between CD59 and other immune molecules and the implications of these interactions in different disease contexts requires comprehensive research.

A: Researchers typically employ various approaches to identify potential compounds for CD59-targeted drug development. These may include the high-throughput screening of chemical libraries to identify molecules that interact with CD59, computational modeling to predict binding affinities, and structure-based drug design. Moreover, researchers may study the natural ligands or endogenous modulators of CD59 to inspire drug development strategies. In some cases, repurposing existing drugs with known safety profiles for CD59 modulation may also be explored.

A: Current approaches to target CD59 include monoclonal antibodies, small molecule inhibitors, and gene therapy. Monoclonal antibodies can bind specifically to CD59, modulating its activity. Small molecule inhibitors aim to interfere with CD59's function. Gene therapy involves introducing or modifying genes to regulate CD59 expression or function.

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