Liposome mediated drug delivery for leukocyte adhesion deficieny I (LAD I): Targeting the mutated gene ITGB2 and expression of CD18 protein
Liposome mediated drug delivery for leukocyte adhesion deficieny I (LAD I): Targeting the mutated gene ITGB2 and expression of CD18 protein
摘要
Leukocyte adhesion deficiency (LAD) I is a disorder caused due to mutations in a gene (ITGB2) located on chromosome 21 and encodes the β2 subunit of the leukocyte integrin molecules. This leads to defects in the adhesion of leukocytes on endothelial cells which further leads to recurrent microbial infections due to a decrease in the immune response. Base Excision Repair Mechanism (BER) is instrumental in repairing damaged DNA by removing mutated/ damaged bases. We have proposed a hypothesis for the treatment of LAD I by making use of the proteins/enzyme complexes responsible for base excision repair mechanism be introduced into the leukocytes via liposomes. This will target the mutated gene in the leukocytes (mostly neutrophils) and DNA repair will occur. The liposomes can be introduced into the patients via intravenous methods.
Leukocyte adhesion deficiency (LAD) I is a disorder caused due to mutations in a gene (ITGB2) located on chromosome 21 and encodes the β2 subunit of the leukocyte integrin molecules. This leads to defects in the adhesion of leukocytes on endothelial cells which further leads to recurrent microbial infections due to a decrease in the immune response. Base Excision Repair Mechanism (BER) is instrumental in repairing damaged DNA by removing mutated/ damaged bases. We have proposed a hypothesis for the treatment of LAD I by making use of the proteins/enzyme complexes responsible for base excision repair mechanism be introduced into the leukocytes via liposomes. This will target the mutated gene in the leukocytes (mostly neutrophils) and DNA repair will occur. The liposomes can be introduced into the patients via intravenous methods.
参考文献24
-
1Akbari M, Otterlei M, Pefia-Diaz J, Aas P A, Kavli B, Liabakk N B, Hagen L, Imai K, Durandy A, Slupphaug G, Krokan H E (2004). Repair of U/G and U/A in DNA by UNG2-associated repair complexes takes place predominantly by short-patch repair both in proliferating and growth-arrested cells. Nucleic Acids Res, 32(18): 5486-5498.
-
2Allen T M, Hansen C B, Guo L S (1993). Subcutaneous administration of liposomes: a comparison with the intravenous and intraperitoneal routes of injection. Biochim Biophys Acta, 1150(1): 9-16.
-
3Anderson D C, Springer T A (1987). Leukocyte adhesion deficiency: an inherited defect in the Mac-l, LFA-1, and p150,95 glycoproteins. Annu Rev Med, 38(1): 175-194.
-
4Amaout A M, Dana N, Gupta S K, Tenen D G, Fathallah D M (1990). Point Mutations Impairing Cell Surface Expression of the Common β Subunit (CD18) in a Patient with Leukocyte Adhesion Molecule (Leu-CAM) Deficiency. American Soc Clin Invest. lnc., 85:977-981.
-
5Chaudhuri J, Alt F W (2004). Class-switch recombination: interplay of transcription, DNA deamination and DNA repair. Nat Rev Immunol, 4(7): 541-552.
-
6Finkelstein M, Weissmann G (1978). The introduction of enzymes into cells by means of liposomes. J Lipid Res, 19(3): 289-303.
-
7Fortini P, Dogliotti E (2007). Base damage and single-strand break repair: mechanisms and functional significance of short- and long- patch repair subpathways. DNA Repair (Amst), 6(4): 398-409.
-
8Fromme J C, Banerjee A, Verdine G L (2004). DNA glycosylase recognition and catalysis. Curr Opin Struct Biol, 14(1): 43-49.
-
9Kishimoto T K, O'Conner K, Springer T A (1989). Leukocyte adhesion deficiency. Aberrant splicing of a conserved integrin sequence causes a moderate deficiency phenotype. J Biol Chem, 264(6): 3588-3595.
-
10Kuhn S H, Gemperli B, Shephard E G, Joubert J R, Weidemann P A, Weissmann G, Finkelstein M C (1983). Interaction of liposomes with human leukocytes in whole blood. Biochim Biophys Acta, 762(1): 119-127.
-
1钱林东,曹兴萍,王继春,张自芳,胡小九.猪细小病毒病和弓形体病的血清学调查[J].畜牧兽医科技信息,2008,24(10):26-27.
-
2马金柱,李军,王北艳,曹宁,崔玉东,李鹏,余丽芸.牛CD18编码全基因特异引物设计与PCR扩增[J].黑龙江八一农垦大学学报,2006,18(3):59-60. 被引量:2
-
3严鸣,毛积芳,钟纪根,何健,朱秋峰,徐仁宝.YFP-CD18融合蛋白在U937细胞株中的表达与鉴定[J].生物技术,2003,13(4):4-6.
-
4ZHU Na,QIAO Ying,ZHANG Di,WANG Wen-juan,LIU Jia,LIU Tian-zhou,MA Tong-hui.Remarkably Decreased CD11b Positive Splenocytes in Aquaporin 3-Null Mice[J].Chemical Research in Chinese Universities,2010,26(2):217-220.
-
5毛景东,刘金华,丁宁,李婷婷,鲁金波,耿万友.CD11b/CD18对中性粒细胞功能的调控研究进展[J].动物医学进展,2014,35(1):106-110. 被引量:5
-
6Errol C Friedberg.A brief history of the DNA repair field[J].Cell Research,2008,18(1):3-7. 被引量:7
-
7钟诚.黑白花奶牛“白细胞粘附缺陷症”(LAD)的分子生物学分析与诊断[J].广西科学,1995,2(2):1-5.
-
8刘召亮,何觉民,陈彪,梁钾贤.绿玉树茎段组织培养再生体系的建立[J].安徽农业科学,2011,39(17):10161-10163. 被引量:9
-
9罗齐寒,赵长林.四川集体林权制度主体改革存在的问题与对策[J].四川林勘设计,2014(3):34-35.
-
10马金柱,崔玉东,王北艳,王龙祥,王凤强,田立志,朱战波,余丽芸.牛白细胞粘附缺陷病携带牛CD18的部分基因序列分析[J].中国兽医杂志,2006,42(9):13-14.