1 CNS. Basic Medical Sciences and Clinics (3) (gene therapy) (central nervous system, CNS) CNS. , CNS (conditionally immortal2

HTML
DOWNLOAD

Μέγεθος: px

Εμφάνιση ξεκινά από τη σελίδα:

Download "1 CNS. Basic Medical Sciences and Clinics (3) (gene therapy) (central nervous system, CNS) CNS. , CNS (conditionally immortal2"

Ἅβραμ Ράγκος
6 χρόνια πριν
Προβολές:

206 Basic Medical Sciences and Clinics 2002122 (3) : 100126325 ( 2002) 0320206207 1 2 1 2 1 3 (11 100083 ; 21 510282) : ; : ; ; :R741105 :A (gene therapy) : ; (central nervous system

1 206 Basic Medical Sciences and Clinics (3) : ( 2002) ( ; ) : ; : ; ; :R :A (gene therapy) : ; (central nervous system CNS) ; ; CNS Π CNS CNS [1 CNS ] (conditionally immortal2 1 CNS ized neural cell) 111 ex vivo 112 in vivo ex vivo in vivo : ( ) DNA (minipump) CNS ex vivo : : ( G ) 3

2 (3) Basic Medical Sciences and Clinics 207 in vivo CNS (HSV2RV) in vivo CNS HSV2RV HSV2RV 2 CNS HSV 211 RNA : pac HSV RNA HSV HSV Moloney HSV : pac BAC ; : ; 22kb ; 150kb ; ; HSV ; HSV HSV ; CNS : (adenovirus Ad) : (lentivirus) DNA 36kb 4 ( human immunodeficiency virus HIV) ( lentivirus2based vector LV) Ad E2a E4 E4 HIV21 (gutless) Ad Ad ( self2inactivating SIN) LV ( ) LV [2 3 CNS ] 21 2 DNA HSV DNA oris : I DNA (herpes simplex virus type 1 HSV21) 152kb DNA DNA 80 HSV ( ) AAV E12E4 Ad : (adeno2asso2 ciated virus AAV)

3 208 Basic Medical Sciences and Clinics (3) 19 AAV CNS : : AAV CNS ; AAV ITRs ITRs mrna ; raav [6 7 ] ; 311 raav Huntington : Huntington ( Huntington s [4 ] disease HD) 213 GABA CNS CNS HD DNA RNA HSVΠAAV (NGF) AdΠEBV HSVΠEBVΠ Bemelmans [8 ] (BD2 AdΠAAV AdΠ NF) Ad Huntington : (lysosomal storage disease LSD) Ad 2 in vivo ( 2glucuronidase GUS) Ad GUS [9 ] AAV Ad [5 ] GUS GUS 3 CNS HD IT15 Huntington BDNF LSD GUS CNS [10 ] Leshch2Nyhan : Leshch2Nyhan (Lesch2 Nyhan disease LND) X

4 (3) Basic Medical Sciences and Clinics 209 Xq ( hypoxanthine2guanine phosphoribosyl2 transferase HPRT) HPRT s disease AD) LND CNS Palella [11 ] HSV 2 ( 2amyloid pro2 HPRT tein 2AP) HPRT LND LND AD : ( Parkinson s disease PD) CNS (choline acetylase ChA) AD ChA PD ChA CNS AD Saille [16 ] bcl22 2 PD : AD (dopamine DA) DA [12 ] ; DA : (amyotrophic lateral sclerosis ALS) (tyrosine hydroxylase TH) DA (superoxide dismutase SOD) TH DA TH ALS BH4 (CNTF) GDNF TH BH4 (BDNF) GTP2cyclohydrolase1 ( IGF21) Haase [13 L2dopa ] DA ALS DA PD Mohajeri [18 ] PD GDNF 6 ALS 18 DA GDNF ( GDNF) DA Azzouz GDNF raav bcl22 SOD DA bcl22 bcl22 DA PD [19 ] : (Alzheimer NGF [15 ] AD Yamada [14 ] bcl22 HSV 313 [17 ] Ad CNTF bcl22 CNS

5 210 Basic Medical Sciences and Clinics (3) 2 50 % CNS 2 CNS [25 ] CNS : : HSV (HSP72) CNS [24 ] Ad [26 CNS GABA ] [20 ] [21 ] [27 ] : rattleboro 314 CNS : Geddes [28 ] Ad Ca 2 + Na + Brattleboro 2 [22 ] [29 ] Ad ( neuronal apoptosis in2 raav bcl22 AAV Leptin obπob CNS hibitory protein NAIP) [23 ] HSV 72KD [24 ] : CNS : [1 ] Costantini LC Bakowska JC Breakefield XO et al. Gene therapy in the CNS[J ]. Gene Ther : [2 ] Englund U Ericson C Rosenblad C et al. The use of a recombinant lentiviral vector for ex vivo gene transfer into the rat CNS[J ]. Neuroreport : [3 ] Kafri T van Praag H Gage FH et al. Lentiviral vectors : reg2 ulated gene expression[j ]. Mol Ther : [4 ] Peel AL Klein RL. Adeno2associated virus vectors : activity and applications in the CNS[J ]. J Neurosci Methods : [5 ] Klein RL Mandel RJ Muzyczka N. Adeno2associated virus vector2mediated gene transfer to somatic cells in the central ner2 vous system[j ]. Adv Virus Res : [6 ] Natsume A Mata M Goss J et al. Bcl22 and GDNF delivered by HSV2mediated gene transfer act additively to protect dopam2 inergic neurons from 62OHDA2induceddegeneration [ J ]. Neurol : Exp [7 ] Berry M Barrett L Seymour L et al. Gene therapy for central nervous system repair[j ]. Curr Opin Mol Ther : [8 ] Bemelmans AP Horellou P Pradier L et al. Brain2derived neurotrophic factor2mediated protection of striatal neurons in an excitotoxic rat model of Huntington s disease as demonstrated by adenoviral gene transfer [J ]. Hum Gene Ther :

6 (3) Basic Medical Sciences and Clinics [ 9 ] Ghodsi A. Extensive beta2glucuronidase activity in murine cen2 tral nervous system after adenovirus2mediated gene tranfer to brain[j ]. Hum Gene Ther : [10 ] Snyder EY Taylor RM Wolfe J H. Neural progenitor cell en2 graftment corrects lysosomal storage throughout the MPS VII mouse brain[j ]. Nature : [ 11 ] Palella TD Hidaka Y Silverman LJ et al. Expression of human HPRT mrna in brains of mice infected with a recom2 binant herpes simplex virus21 vector [J ]. Gene : [12 ] Bjorklund A Kirik D Rosenblad C et al. Towards a neuro2 protective gene therapy for Parkinson s disease : use of adeno2 virus AAV and lentivirus vectors for gene transfer of GDNF to the nigrostriatal system in the rat Parkinsonian model [ J ]. Brain Res : [13 ] Kang UJ Lee WY Chang JW. Gene therapy for Parkinson s disease : determining the genes necessary for optimal dopamine replacement in rat models[j ]. Hum Cell : [14 ] Yamada M Oligino T Mata M et al. Herpes simplex virus vector2mediates expression of Bcl22 prevents 62hydroxydopam2 ine2induced degeneration of neurons in the substantia nigra in vivo[j ]. Proc Natl Acad Sci USA :4078. [15 ] Tuszynski MH Smith DE Roberts J et al. Targeted intrapa2 renchymal delivery of human NGF by gene transfer to the pri2 mate basal forebrain for 3 months does not accelerate beta2 amyloid plaque deposition[j ]. Exp Neurol : [ 16 ] Saille C Marin2P Martinou JC et al. Transgenic murine cortical neurons expressing human bcl22 exhibit increased re2 sistance to amyloid beta2peptide neurotoxicity [ J ]. science : Neuro2 [17 ] Haase G Pettmann B Vigne E et al. Therapeutic benefit of ciliary neurotrophic factor in progressive motor neuropathy de2 pends on the route of delivery[j ]. Ann Neurol : [18 ] Mohajeri MH Figlewicz DA Bohn MC. Intramuscular grafts of myoblasts genetically modified to secrete glial cell line2de2 rived neurotrophic factor prevent motoneuron loss and disease progression in a mouse model of familial amyotrophic lateral sclerosis[j ]. Hum Gene Ther : [19 ] Azzouz M Hottinger A Paterna JC et al. Increased mo2 toneuron survival and improved neuromuscular function in transgenic ALS mice after intraspinal injection of an adeno2as2 sociated virus encoding bcl22[j ]. Hum Mol Genet : [20 ] Adachi Y Tamiya T Ichikawa T et al. Experimental gene therapy for brain tumors using adenovirus2mediated transfer of cytosine deaminase and uracil phosphoribosyltransferase gene with 52fluorocytosine [J ]. Hum Gene Ther : [21 ] Im SA Gomez2Manzano C Fueyo J et al. Antiangiogenesis treatment for gliomas : transfer of antisense2vascular endothelial growth factor inhibits tumor growth in vivo [J ]. Cancer Res : [22 ] Shimazaki K Urabe M Monahan J et al. Adeno2associated virus vector2mediated bcl22 gene transfer into post2ischemic gerbil brain in vivo : prospects for gene therapy of ischemia2in2 duced neuronaldeath[j ]. Gene Ther : [23 ] Xu DG Crocker SJ Doucet JP et al. Elevation of neuronal expression of NAIP reduces ischemic damage in the rat hipp2 ocampus[j ]. Nature Med : [24 ] Yenari MA Fink SL Sun GH et al. Gene therapy with HSP72 is neuroprotective in rat models of stroke and epilepsy [J ]. Ann Neurol : [25 ] Finegold AA Mannes AJ Iadarola MJ. A paracrine paradigm for in vivo gene therapy in the central nervous system : treat2 ment of chronic pain[j ]. Hum Gene Ther : [26 ] Robert JJ Bouilleret V Ridoux V et al. Adenovirus2mediat2 ed transfer of a functional GAD gene into nerve cells : potential for the treatment of neurological diseases [ J ]. Gene Ther : [ 27 ] Zhang LX Li XL Smith MA et al. Lipofectin2facilitated transfer of cholecystokinin gene corrects behavioral abnormali2 ties of rats with audiogenic seizures[j ]. Neuroscience : [28 ] Geddes BJ Harding TC Lightman et al. Long2term gene therapy in the CNS: reversal of hypothalamic diabetes inspidus in the Bratteboro rat by using an adenovirus expressing argin2 ine vasopressin[j ]. Nature Med : [29 ] Dhillon H Kalra SP Prima V et al. Central leptin gene therapy suppresses body weight gain adiposity and serum in2 sulin without affecting food consumption in normal rats : a long2 term study[j ]. Regul Pept : ( 218 )

7 218 Basic Medical Sciences and Clinics (3) 388. [39 ] Svendsen CN Caldwell MA Shen J et al. Long2term surviv2 al of human central nervous system progenitor cells transplanted into a rat model of Parkinson s disease [J ]. Exp Neurol : [40 ] Nishino H Hida H Takei N et al. Mesencephalic neural stem (progenitor) cells develop to dopaminergic neurons more strongly in dopamine2depleted striatum than in intact striatum [J ]. Exp Neurol : [41 ] Fricker J. Human neural stem cells on trial for Parkinson s disease[j ]. Mol Med Today : 144. [42 ] Toda H Takahashi J Iwakami N et al. Grafting neural stem cells improved the impaired spatial recognition in ischemic rats [J ]. Neurosci Letters : [43 ] Benedetti S Piroia B Pollo B. Gene therapy of experimental brain tumors using neural progenitor cells [J ]. Nature Medi2 cine : [44 ] Aboody KS Brown A Raioov NG et at. From the cover : neural stem cells display extensive tropism for pathology in adult brain : evidence from intracranial gliomas[j ]. Proc Natl Acad Sci USA : [45 ] Pincus DW Goodman RR Fraser RAR et al. Neural stem and progenitor cells : a strategy for gene therapy and brain re2 pair[j ]. Neurosurgery : [46 ] Kalyani AJ Rao MS. Cell lineage in the developing neural tube[j ]. Biochem Cell Biol : Progress in neural stem cells WANG Xuan WANG Kun WANG Xiao2min (Neuroscience Research Institute Peking University Beijing China) Abstract : Recently the research methods for stem cells from central nervous system and the clinical application have at2 tracted attention of CNS study. In this review the finding of neural stem cells new research techniques and therapeutic effects on the CNS disorders such as neurodegeneration diseases ischema injury and tumors by applying neural stem cells are introduced. Key words : neural stem cells ; neuroregeneration ; cell transplantation ( 211 ) The gene therapy of central nervous system disorders ZHANG Wang2ming NIU Dong2bin XU Ru2xiang et al (Neuroscience Research Institute Peking University Beijing China) Abstract : Gene therapy is a potential and new methods of treating many neurological diseases that were considered re2 fractory to current conventional treatments. By injection of viral vectors or transplantation of genetically engineered cells into specific sites of the brain the development of technologies for delivery of foreign genes into brain opened the field to promising treatments for CNS disorders. But the development of gene therapy for neurological diseases represents a more complex problem than that for other systemic disorders. Incomplete characterization of target organs ( brain and spinal cord) and additional challenges such as post2mitotic cells heterogeneity of cell types and circuits and limited access all contribute to the difficulties. For this reason this report provides an update outline of gene therapy in CNS and re2 views current researches in this filed. Key words : gene therapy ; central nervous system ; viral vectors Corresponding author : Wang Xiao2min

Σχετικά έγγραφα

1992 Reynolds Richards

1992 Reynolds Richards 212 Basic Medical Sciences and Clinics 2002122 (3) : 100126325 ( 2002) 0320212207 3 ( 100083) : : ; ; :R741105 :A (central nervous system [1 CNS) ] 1998 19 20 James Thomson John Gearhart (embryonic stem