See also specific diseases for references to CRegs  and Drug Targetting under Pharmacology

CRegs for the Treatment of Diseases

CR1: Levin (US 6,169,068) teaches a method for treating diseases involving complment by pulmonary administration of complement inhibitor proteins such as a soluble complement receptor type 1 (sCR1). 

CD46 (MCP): Sweigard teaches that adenovirus mediated delivery of CD46 attenuates the AP pathway and has implications for age related macular degeneration (Gene Therapy 18, 613-621 (2011).

CD59: 

–AMD: Bora discloses that a recombinant membrane targeted form of CD59 inhibits the growth of choroidal neovascular complex in mice (J Biol Chem 285, 2010, 33826-33833). Cashman also discloses that a non membrane-targeted human soluble CD59 attenuates choroidal neovascularization in a model of age related macular degeneration (PLOS ONE, e 19078, 6(4) 2011, 1-9).

Ramo evaluates adenovius delivered human CD59 as a potential therapy for AMD in a model of human membrane attack complex formation on murin RPE (Invest Opthalmol Vis Sci 49(9): 4126-4136 (2008).

–Atherosclerosis: Wu teaches that CD59 protects against atherosclerosis by restricting the formation of complement membrane atttack complex (Circ Res 104: 550-558), 2009). 

CReg Fusion Constructs for the Treatment of Diseases

–CD55 (DAF) and CD46 (MCP) fusion proteins: have been shown to be more effective thatn DAF, MCP or DAF and MCP at inhibiting C3 deposition via the alternative pathway. Chimeric proteins in which MCP, DAF and MCP-DAF hybrids have also been produced with cell surface loalizing domains which target the molecules to cell surfaces, thereby increasing the concentraiton of these molecules on cell surfaces where they can act to inhibit complement-mediated cell lysis. MCP-DAF hybrids may contain the entire sequence of both molecules or may contain just the SCR regions form each MCP and DAF.  (Innis, WO 96/34965). Ko (US 5,679,546 and 5,851,528) and Wijesuriya (US 2006/0154336) also disclose chimeric genes and proteins which express the biological activities of both MCP and DAF. The proteins are referred to as “Complement Activation Blocker” (CAB) proteins.

–CD46 and CD55 and CD59 fusion construct: Kumar-Singh (US 13/692734) teaches a construct having the complement regulatory domains of each of CD46, C55 and CD59 with the native secretory signal of CD59 at the N-terminus. The SCR domains of CD46 and CD55 are involved in complement control and the serine threonine proline (STP) region is heavily glycosylated. The majrority of amino acids of the STP region were removed and the amino acid sequences of the full-lenght SCR doamins for each regulator was retained. Glycine linkers were added to separate each complement regulatory domain. 

–CR2 fusion constructs with CRegs: (see Complement Receptor Drug Targetting under Pharmacology)

–DAF-CD59: Fodeor (5627264) teaches chimeric complement inhibitors having C3 inhibitory activity and a second functional domain having C5b-9 inhbitory activity such as DAF-CD59 fusion consructs.

–Antibody-CD59 constructs (see also drug delivery under pharmacology): Zhang (J. Clinical Invest. 1999, 103(1)) teaches antibody-CD59 chimeric fusion proteinswhich provided targeted cells with effecitve protection from complement mediated lysis.