Chemistry: molecular biology and microbiology – Treatment of micro-organisms or enzymes with electrical or... – Modification of viruses
Patent
1998-09-01
2000-07-18
Raymond, Richard L.
Chemistry: molecular biology and microbiology
Treatment of micro-organisms or enzymes with electrical or...
Modification of viruses
435 2, 435236, 604 4, 540145, C12N 1300, C12N 704, A61M 3700
Patent
active
060905999
DESCRIPTION:
BRIEF SUMMARY
This work is supported in part by award no. 2RO1-HL41221 from the National Heart, Lung and Blood Institute and award no. PO1-CA48735 from the National Cancer Institute.
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention concerns a process for rendering a red blood cell-containing composition substantially free of an extracellular or intracellular virus which may be present therein without substantially disrupting the red blood cells or labile proteins or other valuable biological components also contained therein.
2. Description of the Related Art
The use of blood for transfusion is safer nowadays than it has ever been. This is particularly true for coagulation factor concentrates and plasma. These blood products have been made completely safe with respect to transmission of hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV) by implementation of virucidal procedures. See B. Cuthbertson et al., "Viral contamination of human plasma and procedures for preventing virus transmission by plasma products," In: Blood Separation and Plasma Fractionation, ed. by R. J. Harris, Wiley-Liss, New York, 1991, pages 385-435; and A. M. Prince et al., Eur. J. Epidemiol., 3: 103-118 (1987).
However, transfusion of cellular blood components is still associated with risk of infection in spite of improvement in donor selection and serological testing. See P. Kuhnl et al., "Reduction of virus load in blood donations by screening methods," In: Virus Inactivation in Plasma Products, ed. by J. J. Morganthaler, Karger Press, Basel, 1989, pages 9-22. As a result, efforts are now focused on sterilizing red blood cell (RBC) and platelet concentrates. The most promising results were obtained with the use of photochemical approaches. For a recent review, see E. Ben-Hur and B. Horowitz, "Advances in photochemical approaches for blood sterilization," Photochem. Photobiol., 62: 383-388 (1995).
For virus inactivation in RBC concentrates use has been made of phthalocyanines. See, B. Horowitz et al., "Inactivation of viruses in blood with aluminum phthalocyanine derivatives," Transfusion, 31: 102-108 (1991); and E. Ben-Hur et al., "Photodynamic inactivation of retroviruses by phthalocyanines: the effect of sulfonation, metal ligand and fluoride," J. Photochem. Photobiol. B:Biol., 13: 145-152 (1992).
The phthalocyanines are efficient photodynamic sensitizers with maximum absorption in the far red (650-700 nm). Virus inactivation appears to be mediated by disruption of the virus envelope. See Z. Smetana et al., "Photodynamic inactivation of herpes viruses with phthalocyanine derivatives," J. Photochem. Photobiol. B:Biol., 22: 37-43 (1994).
However, the RBC membrane can also be damaged in the process. See E. Ben-Hur et al., "Photohemolysis of human erythrocytes induced by aluminum phthalocyanine tetrasulfonate," Cancer Lett., 30: 321-327 (1986); and E. Ben-Hur et al., "Inhibition of phthalocyanine-sensitized photohemolysis of human erythrocytes by quercetin," Photochem. Photobiol., 57: 984-988 (1993).
Thus, it was necessary to enhance the specificity of the process. This was achieved by various approaches. First, structure-activity relationships were sought. See E. Ben-Hur et al., "Phthalocyanine-induced photohemolysis: structure-activity relationship and the effect of fluoride," Photochem. Photobiol., 58: 351-355 (1993); and S. Rywkin et al., "New phthalocyanines for photodynamic virus inactivation in red blood cells," Photochem. Photobiol., 60: 165-170 (1994). The result was the identification of a silicon phthalocyanine Pc 4 having maximal virucidal activity and minimal RBC damage. See E. Ben-Hur et al., "Virus inactivation in red cell concentrates by photosensitization with phthalocyanines: protection of red cells but not of vesicular stomatitis virus with a water-soluble analogue of vitamin E," Transfusion, 35: 401-406 (1995).
Second, quenchers of reactive oxygen species were added during light exposure. These include mannitol [S. Rywkin et al., "Importance of type I and type II
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New York Blood Center Inc.
Raymond Richard L.
Sripada Pavanaram K
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