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Engineered opsonins for pathogen detection and treatment

An opsonin, collagen technology, applied in the systemic field of pathogens, can solve problems affecting the complement system and agglutination pathways, vasculature and organ damage, death, etc.

Active Publication Date: 2018-07-06
PRESIDENT & FELLOWS OF HARVARD COLLEGE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

This immune response causes widespread activation of acute phase proteins, affects the complement system and the coagulation pathway, and then causes damage to the vasculature and organs
Various neuroendocrine counter-regulatory systems are also activated, often complicating matters
Even with immediate and vigorous treatment, it can develop multiple organ dysfunction syndrome and eventually die

Method used

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  • Engineered opsonins for pathogen detection and treatment
  • Engineered opsonins for pathogen detection and treatment
  • Engineered opsonins for pathogen detection and treatment

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0107] Construction and expression of embodiment 1.FcMBL.81

[0108] An embodiment of an engineered construct MBL for use as a general opsonin in diagnostic and therapeutic applications can be constructed using the "neck" and "lectin" domains of MBL. The proline at position 81 (as defined in Structural Bioinformatics Research Center, Protein Data Bank Structure File 1HUP) was chosen as the N-terminal point at which the lectin sequence begins. This localized downstream (C-terminus) of the lectin molecule is fused to the human Fc portion γ1 (Fcγ). exist image 3 A diagram of the engineered lectin construct is shown in . exist Figure 4 A schematic diagram of the cloned Fc portion is shown in .

[0109] The amino acids of this construct include the following residues:

[0110] Fc protein sequence:

[0111]

[0112] MBL.81 protein sequence (this sequence includes the coiled-coil neck region and carbohydrate recognition domain (CRD) of human MBL):

[0113]

[0114] Fc-...

Embodiment 2

[0118] Example 2. Comparison of Fc MBL.81 constructs with full length MBL for binding to yeast.

[0119] Approximately 5.5 million Candida albicans yeast cells were inoculated with varying numbers of MBL beads coated with wild-type full-length MBL (hexamer of trimers) or Fc MBL.81. like Figure 9 As shown in the figure, 18 million wild-type full-length MBL or Fc MBL.81 beads bound all 5.5 million fungal cells. This example demonstrates that Fc MBL.81 beads are as active as wild-type full-length MBL beads in binding to C. albicans.

[0120]

[0121]

[0122]

[0123]

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Abstract

The present invention provides engineered molecular opsonins that can be used to bind biological pathogens or identify subclasses or specific pathogen species for use in patients suffering from infectious diseases, blood-borne infections or sepsis In devices and systems for treatment and diagnosis. One aspect of the present invention provides mannose-binding lectin (MBL), which is an abundant natural serum protein that is part of the innate immune system. The ability of this protein lectin to bind to surface molecules on nearly all kinds of biological pathogens (viruses, bacteria, fungi, protozoa) makes engineered forms of MBL extremely useful in the diagnosis and treatment of infectious diseases and sepsis.

Description

[0001] Cross References to Related Applications [0002] This application claims the benefit of US Provisional Application No. 61 / 296,222, filed January 19, 2010, the contents of which are hereby incorporated by reference in their entirety. technical field [0003] The present invention relates to molecular immunology, microbial pathogens, and systems for detecting and / or removing pathogens in fluids, including bodily fluids such as blood. More specifically, for example, the present invention provides engineered molecular opsonins that can be used to bind biological pathogens or recognize subclasses or specific pathogen species, thereby being useful in the treatment of patients with infectious diseases, blood-borne infections or sepsis. Devices and systems for the treatment and diagnosis of diseased patients. Background technique [0004] In the United States, sepsis is the second leading cause of death among non-coronary ICU patients and the tenth most common cause of deat...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07K19/00
CPCC07K2319/30C07K14/4726A61P31/00A61P31/04A61P43/00A61P7/00A61K38/00Y02A50/30G01N33/56961C07K16/44C07K17/00G01N2333/40C07K2317/66C07K2317/53G01N33/50G01N33/569G01N33/56911G01N27/745
Inventor 米歇尔·舒普尔杰弗里·查尔斯·韦唐纳德·E·英堡
Owner PRESIDENT & FELLOWS OF HARVARD COLLEGE
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