Brain drug targeting and gene technologies

被引:43
作者
Pardridge, WM [1 ]
机构
[1] Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90095 USA
关键词
blood-brain barrier; gene therapy; brain-derived neurotrophic factor; epidermal growth factor; genomics;
D O I
10.1254/jjp.87.97
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Brain drug targeting technology is based on the application of four gene technologies that enable the delivery of drugs or genes across the blood-brain barrier (BBB) in vivo. I) Genetic engineering is used to produce humanized monoclonal antibodies that target endogenous BBB transporters and act as vectors for delivery of drugs or genes to the human brain. The conjugate of a neurotherapeutic and a BBB transport vector is called a chimeric peptide. Epidermal growth factor chimeric peptides have been used for neuroimaging of brain cancer. Brain-derived neutrophic factor chimeric peptides have marked neuroprotective effects in brain stroke models. II) Imaging gene expression in the brain in vivo is possible with sequence-specific antisense radiopharmaceuticals, which are conjugated to BBB drug targeting vectors. III) Brain gene targeting technology enables widespread expression of an exogenous gene throughout the central nervous system following an intravenous injection of a non-viral therapeutic gene. IV) A BBB genomics program enables the future discovery of novel transport systems expressed at the BBB. These transporters may be carrier-mediated transport systems, active efflux transporters, or receptor-mediated transcytosis systems. The future discovery of novel BBB transport systems and the application of brain drug targeting technology will enable the delivery to the brain of virtually any neurotherapeutic, including small molecules, large molecules and gene medicines.
引用
收藏
页码:97 / 103
页数:7
相关论文
共 25 条
  • [1] Transport across the primate blood-brain barrier of a genetically engineered chimeric monoclonal antibody to the human insulin receptor
    Coloma, MJ
    Lee, HJ
    Kurihara, A
    Landaw, EM
    Boado, RJ
    Morrison, SL
    Pardridge, WM
    [J]. PHARMACEUTICAL RESEARCH, 2000, 17 (03) : 266 - 274
  • [2] Retention of biologic activity of human epidermal growth factor following conjugation to a blood-brain barrier drug delivery vector via an extended poly(ethylene glycol) linker
    Deguchi, Y
    Kurihara, A
    Pardridge, WM
    [J]. BIOCONJUGATE CHEMISTRY, 1999, 10 (01) : 32 - 37
  • [3] Suppression subtractive hybridization: A method for generating differentially regulated or tissue-specific cDNA probes and libraries
    Diatchenko, L
    Lau, YFC
    Campbell, AP
    Chenchik, A
    Moqadam, F
    Huang, B
    Lukyanov, S
    Lukyanov, K
    Gurskaya, N
    Sverdlov, ED
    Siebert, PD
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (12) : 6025 - 6030
  • [4] Drug discovery: A historical perspective
    Drews, J
    [J]. SCIENCE, 2000, 287 (5460) : 1960 - 1964
  • [5] Epidermal growth factor radiopharmaceuticals:: 111In chelation, conjugation to a blood-brain barrier delivery vector via a biotin-polyethylene linker, pharacokinetics, and in vivo imaging of experimental brain tumors
    Kurihara, A
    Deguchi, Y
    Pardridge, WM
    [J]. BIOCONJUGATE CHEMISTRY, 1999, 10 (03) : 502 - 511
  • [6] Kurihara A, 1999, CANCER RES, V59, P6159
  • [7] Efflux transport systems for drugs at the blood-brain barrier and blood-cerebrospinal fluid barrier (Part 1)
    Kusuhara, H
    Sugiyama, Y
    [J]. DRUG DISCOVERY TODAY, 2001, 6 (03) : 150 - 156
  • [8] Genetically engineered brain drug delivery vectors:: cloning, expression and in vivo application of an anti-transferrin receptor single chain antibody-streptavidin fusion gene and protein
    Li, JY
    Sugimura, K
    Boado, RJ
    Lee, HJ
    Zhang, C
    Duebel, S
    Pardridge, WM
    [J]. PROTEIN ENGINEERING, 1999, 12 (09): : 787 - 796
  • [9] Blood-brain barrier genomics
    Li, JY
    Boado, RJ
    Pardridge, WM
    [J]. JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 2001, 21 (01) : 61 - 68
  • [10] McMaster G, 2000, MED RES REV, V20, P187