01. Gene therapy Boulikas.pdf - Gene therapy & Molecular Biology

More documents

Recommendations

Info

LNCaP; delivery of this recombinant adenovirus resulted in cytotoxicity to the DU145 and LNCaP, but not PC-3, cell lines and reduced the clonogenic capacity of DU145 cells cultured alone or mixed with various ratios of irradiated human bone marrow. This finding led to a strategy for effectively reducing DU145 and erbB-2positive primary prostate tumor contamination in bone marrow cultures (Kim et al, 1997). Delivery of an antierbB-2 single chain (sFv) antibody gene for previously treated ovarian and extraovarian cancer patients is in clinical trials using adenoviral gene delivery (protocol #133). A luciferase expression vector (pRSVLuc) noncovalently linked to a humanized HER2 antibody (rhuMAbHER2) covalently modified with poly-L-lysine bridges was able to direct gene transfer to HER2 expressing cells in vitro (Foster and Kern, 1997). A targeting gene therapy approach for hematopoietic stem/progenitor cells has been directed to cell lines expressing the c-kit receptor; plasmid DNA containing a luciferase reporter gene was condensed with polylysine covalently linked to streptavidin (which binds biotinylated ligand) and with polylysine covalently linked to adenovirus (to achieve endosomal lysis) with the final addition of biotinylated steel factor; omission of the adenovirus endosomalytic agent from the vector resulted in the loss of gene expression (Schwarzenberger et al, 1996). Systemic administration of a c-fos antisense, regulated by mouse mammary tumor virus (MMTV) control elements in a retroviral vector, showed expression only in breast epithelium although the vector could be detected in several tissues thus supporting targeting to MMTVregulated tissues (Arteaga and Holt, 1996). Liposomes coated with polyethyleneglycol (PEG) can be efficiently targeted to tumor cells that express folate receptors (KB cells) via conjugation of folate to a PEG spacer of 25 nm in length; shorter PEG spacers were not efficient in mediating binding of the liposomes to KB cells (Lee and Low, 1995). Neri and coworkers (1997) were able to target an angiogenesis-associated oncofetal fibronectin (B-FN) isoform by affinity-matured recombinant antibody fragments. B-FN is present in vessels of neoplastic tissues during angiogenesis but is absent from mature vessels and could provide a target for diagnostic imaging and therapy of cancer. Phage display libraries were screened to isolate human antibody fragments able to recognize this isoform across species; imaging of F9 murine teratocarcinomas grafted in nude mice is shown on Figures 8 and 9. H. Targeted gene delivery with peptidedisplaying phages Boulikas: An overview on gene therapy 26 Development of methods to display and select collections of peptides specific for binding a target provide valuable tools to identification of peptide drugs; peptides could be selected for binding biological targets including cell surface receptor molecules, DNA, antibodies, or whole cells. The technique of peptide-displaying phages has been developed for targeted gene delivery. Selection of cell surface-binding peptides, ideally specific for each type of cell in the human body, will be used for incorporation into gene delivery vehicles to achieve the long-searched tissue specificity of the vector (reviewed by Russell, 1996). Development of the random peptide library as a source of specific protein binding molecules (Devlin et al, 1990) and exposure of random peptides on the surface of phages (Cwirla et al, 1990) has been the catalyst for progress in this promising field. Libraries of random 8 to 12 amino acid peptides expressed on the N-terminus of the pIII protein of the fd phage or on the N-terminus of the pVIII major coat protein of the same phage have been selected that bind the extracellular domain of human IL-1 receptor; screening was against immobilized IL-1 receptor extracellular domain. Two families of peptides could act as antagonists blocking triggering of the IL-1 signaling pathway; because IL-1 levels become elevated in autoimmune and inflammatory disorders, these peptide antagonists of IL-1 receptor could provide novel drugs for these diseases (Yanofsky et al, 1996). Phages displaying known integrin-binding peptides have been shown to bind and enter mammalian cells (Hart et al, 1994). A peptide antagonist to thrombin receptor has been identified using phage display (Doorbar and Winter, 1994). Production of cell-targeting ligands has been achieved by cell-binding peptides specific for different cell types in culture; these peptides are selected through six rounds of binding (and amplification of phage clones) to a particular cell type from random peptide-presenting phage libraries; the selected peptides are apparently recognizing specific surface receptor molecules. For example, the 20mer peptide KTLTLEAALRNAWLREVGLK has been selected for its high affinity for PEA10 mouse fibroblast cells binding 1000 more efficiently to the cells than random peptides (Barry et al, 1996). IX. Gene delivery with polymers, peptides and other means A. Delivery of transferrin-polylysine-DNA complexes A number of polymers have been tested and shown to enhance significantly the transfection efficiency of plasmids but also of viruses; the enhancement in transfection results from a facilitation in the interaction of
plasmids with the cell surface, transport to endosomes, release to the cytoplasm, and in some cases nuclear import (reviewed by Behr, 1994). Figure 8. Role of antibody valence. → Targeting of fluorescently-labeled antibody fragments to the F9 murine teratocarcinoma grafted in nude mice using the monomeric scFv(CGS-1) and dimeric scFv(CGS-1) 2 directed to oncofetal fibronectin; the dimeric scFv(D1.3) 2 with a binding specificity to lysozyme was used as a negative control. t: tumor; b: bladder. From Neri D, Carnemolla B, Nissim A, Leprini A, Querze G, Balza E, Pini A, Tarli L, Halin C, Neri P, Zardi L, Winter G (1997) Targeting by affinity-matured recombinant antibody fragments of an angiogenesis associated fibronectin isoform. Nat Biotechnol 15, 1271-1275. Reproduced with the kind permission of the authors (Dario Neri, Inst for Mol Biology and Biophysics, Zürich) and Nature America, Inc. Gene Therapy and Molecular Biology Vol 1, page 27 27 ← Figure 9. Role of antibody affinity. Targeting of fluorescently-labeled antibody fragments to the F9 murine teratocarcinoma grafted in nude mice using the affinity-matured scFv(CGS-2) and the lower affinity scFv(28SI) directed to the same epitope of oncofetal fibronectin; Tte dimeric scFv(D1.3) 2 with a binding specificity to lysozyme was used as a negative control. t: tumor; b: bladder. From Neri D, Carnemolla B, Nissim A, Leprini A, Querze G, Balza E, Pini A, Tarli L, Halin C, Neri P, Zardi L, Winter G (1997) Targeting by affinity-matured recombinant antibody fragments of an angiogenesis associated fibronectin isoform. Nat Biotechnol 15, 1271-1275. Reproduced with the kind permission of the authors (Dario Neri, Inst for Mol Biology and Biophysics, Zürich) and Nature America, Inc.
Page 1 and 2: Gene Ther Mol Biol Vol 1, 1-172. Ma
Page 3 and 4: I. Introduction Monumental progress
Page 5 and 6: The use of retroviral vectors in hu
Page 7 and 8: displaying the cleavable EGF domain
Page 9 and 10: molecules in the nucleus (Lowe and
Page 11 and 12: sensitive mutations which allow pro
Page 13 and 14: processed as described in panel A s
Page 15 and 16: On the contrary, the payload capaci
Page 17 and 18: in K562 human erythroleukemia cells
Page 19 and 20: defective HSV virus (DeLuca and Sch
Page 21 and 22: complex into the cytosol from the e
Page 23 and 24: Gene Therapy and Molecular Biology
Page 25: delivered by Sendai virus-liposome
Page 29 and 30: infected by adenovirus alone; infec
Page 33 and 34: B. Transcription factor binding sit
Page 35 and 36: A closely related family of ubiquit
Page 37 and 38: cells. I-CreI is a member of this c
Page 41 and 42: C. Considerations of chromatin stru
Page 45 and 46: A. The molecular basis of cancer im
Page 47 and 48: fragments, or heat shock proteins c
Page 49 and 50: ecombinant vaccinia virus expressin
Page 51 and 52: HIV-1 envelope DNA construct develo
Page 53 and 54: inding sites A GYYY oriented in opp
Page 57 and 58: Prives, 1994). Whereas the wild-typ
Page 59 and 60: mutant p53 (mutations on p53 are wi
Page 61 and 62: master regulator of the cell cycle
Page 63 and 64: Work from several groups has shown
Page 65 and 66: chromatin condensation, drop in pH,
Page 67 and 68: Figure 23. A pathway leading to the
Page 69 and 70: Excessive necrotic death in cells o
Page 71 and 72: implantation, and similar processes
Page 73 and 74: normal cells in the surroundings. T
Page 77 and 78:
Gene Therapy and Molecular Biology
Page 79 and 80:
A bicistronic retroviral vector (Ha
Page 81 and 82:
C. Antisense ras gene transfer for
Page 83 and 84:
equal to 6.0 showed S1 hyperreactiv
Page 85 and 86:
protein (e.g. Smith et al, 1995; Fo
Page 87 and 88:
transduced primary mouse fibroblast
Page 89 and 90:
IL-1 - receptor antagonist protein
Page 91 and 92:
p53 lung cancer retroviru s MHC cla
Page 93 and 94:
Page 95 and 96:
designed by immunization with porti
Page 97 and 98:
Isolation of an RNA aptamer that ca
Page 99 and 100:
induction of human apoE in neonate
Page 101 and 102:
atrium in heart, endothelial cells
Page 103 and 104:
which eliminated tumors in small an
Page 105 and 106:
C. Transfer of other genes against
Page 107 and 108:
Page 109 and 110:
significant reduction in neointima
Page 111 and 112:
(Prehn et al, 1996); this implies a
Page 113 and 114:
B. Approaches to gene therapy of RA
Page 115 and 116:
of human immunoglobulin and antigen
Page 117 and 118:
A. Etiology and mechanisms of destr
Page 119 and 120:
Page 121 and 122:
However, CsA also inhibits the acti
Page 123 and 124:
The peptide kinin, after binding to
Page 125 and 126:
intake when administered to adrenal
Page 127 and 128:
Introgen Therapeutics (Austin and H
Page 129 and 130:
When a subfragment of only 513 bp o
Page 131 and 132:
Armentano D, Zabner J, Sacks C, Soo
Page 133 and 134:
Brady HJM, Miles CG, Pennington DJ,
Page 135 and 136:
Chen J, Stickles RJ, Daichendt KA (
Page 137 and 138:
Day ML, Wu S, Basler JW (1993) Pros
Page 139 and 140:
Farmer G, Bargonetti J, Zhu H, Frie
Page 141 and 142:
Giovannangeli C, Perrouault L, Escu
Page 143 and 144:
the neoplastic phenotype by replace
Page 145 and 146:
integrate in a site-specific fashio
Page 147 and 148:
Li R, Waga S, Hannon GJ, Beach D, S
Page 149 and 150:
adiation-induced apoptosis in the g
Page 151 and 152:
Nakaya T, Iwai S, Fujinaga K, Sato
Page 153 and 154:
Polyak K, Xia Y, Zweier JL, Kinzler
Page 155 and 156:
macrophages from simian immunodefic
Page 157 and 158:
intimal hyperplasia in a rat caroti
Page 159 and 160:
Trono D, Feinberg MB, Baltimore D (
Page 161 and 162:
Wattiaux R, Jadot M, Warnier-Pirott
Page 163 and 164:
similar to mammalian interleukin-1
Page 165 and 166:
Page 167 and 168:
24. Gene Marking /Infectious Diseas
Page 169 and 170:
Drug 50. Gene Therapy /Phase I /Can
Page 171 and 172:
76. Gene Therapy /Phase I /Cancer /
Page 173 and 174:
99. Gene Therapy /Phase II /Cancer
Page 175 and 176:
120. Gene Therapy /Phase I /Monogen
Page 177 and 178:
Page 179 and 180:
cancer not specified) /Immunotherap
show all

01. Gene therapy Boulikas.pdf - Gene therapy & Molecular Biology

Create successful ePaper yourself

Delete template?

Save as template?