Peroral gene therapy of lactose intolerance using an adeno-associated virus vector

被引:110
作者
During, MJ
Xu, RL
Young, D
Kaplitt, MG
Sherwin, RS
Leone, P
机构
[1] Univ Auckland, Sch Med, Dept Mol Med, Auckland, New Zealand
[2] Thomas Jefferson Univ, Jefferson Med Coll, Dept Neurosurg, CNS Gene Therapy Ctr, Philadelphia, PA 19107 USA
[3] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06520 USA
[4] Yale Univ, Sch Med, Dept Neurosurg, New Haven, CT 06520 USA
[5] Rockefeller Univ, Dept Neurobiol, New York, NY 10021 USA
关键词
D O I
10.1038/2625
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Gene therapy is usually reserved for severe and medically refractory disorders because of the toxicity, potential long-term risks and invasiveness of most gene transfer protocols. Here we show that an orally administered adeno-associated viral vector leads to persistent expression of a beta-galactosidase transgene in both gut epithelial and lamina propria cells, and that this approach results in long-term phenotypic recovery in an animal model of lactose intolerance. A gene 'pill' associated with highly efficient and stable gene expression might be a practical and cost-effective strategy for even relatively mild disorders, such as lactase deficiency.
引用
收藏
页码:1131 / 1135
页数:5
相关论文
共 23 条
  • [1] Berns K I, 1979, Adv Virus Res, V25, P407, DOI 10.1016/S0065-3527(08)60574-6
  • [2] OSTEOPOROSIS INTESTINAL LACTASE DEFICIENCY AND LOW DIETARY CALCIUM INTAKE
    BIRGE, SJ
    KEUTMANN, HT
    CUATRECASAS, P
    WHEDON, GD
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 1967, 276 (08) : 445 - +
  • [3] NEW INSIGHTS INTO LACTASE AND GLYCOSYLCERAMIDASE ACTIVITIES OF RAT LACTASE-PHLORIZIN HYDROLASE
    BULLER, HA
    VANWASSENAER, AG
    RAGHAVAN, S
    MONTGOMERY, RK
    SYBICKI, MA
    GRAND, RJ
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY, 1989, 257 (04): : G616 - G623
  • [4] Oral somatic transgene vaccination using attenuated S-typhimurium
    Darji, A
    Guzman, CA
    Gerstel, B
    Wachholz, P
    Timmis, KN
    Wehland, J
    Chakraborty, T
    Weiss, S
    [J]. CELL, 1997, 91 (06) : 765 - 775
  • [5] GLUCOSE MODULATES RAT SUBSTANTIA-NIGRA GABA RELEASE IN-VIVO VIA ATP-SENSITIVE POTASSIUM CHANNELS
    DURING, MJ
    LEONE, P
    DAVIS, KE
    KERR, D
    SHERWIN, RS
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 1995, 95 (05) : 2403 - 2408
  • [6] FLATZ G, 1987, ADV HUM GENET, V16, P1
  • [7] Lactose intolerance associated with fractures of weight-bearing bones in Finnish women aged 38-57 years
    Honkanen, R
    Kröger, H
    Alhava, E
    Turpeinen, P
    Tuppurainen, M
    Saarikoski, S
    [J]. BONE, 1997, 21 (06) : 473 - 477
  • [8] PREPROENKEPHALIN PROMOTER YIELDS REGION-SPECIFIC AND LONG-TERM EXPRESSION IN ADULT BRAIN AFTER DIRECT IN-VIVO GENE-TRANSFER VIA A DEFECTIVE HERPES-SIMPLEX VIRAL VECTOR
    KAPLITT, MG
    KWONG, AD
    KLEOPOULOS, SP
    MOBBS, CV
    RABKIN, SD
    PFAFF, DW
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (19) : 8979 - 8983
  • [9] LONG-TERM GENE-EXPRESSION AND PHENOTYPIC CORRECTION USING ADENOASSOCIATED VIRUS VECTORS IN THE MAMMALIAN BRAIN
    KAPLITT, MG
    LEONE, P
    SAMULSKI, RJ
    XIAO, X
    PFAFF, DW
    OMALLEY, KL
    DURING, MJ
    [J]. NATURE GENETICS, 1994, 8 (02) : 148 - 154
  • [10] LISKER R, 1975, AM J HUM GENET, V27, P662