scholarly journals HSV-1-Based Vectors for Gene Therapy of Neurological Diseases and Brain Tumors: Part I. HSV-1 Structure, Replication and Pathogenesis

Neoplasia ◽  
1999 ◽  
Vol 1 (5) ◽  
pp. 387-401 ◽  
Author(s):  
Andreas Jacobs ◽  
Xandra O. Breakefield ◽  
Cornel Fraefel
Keyword(s):  
Gene Therapy ◽  
Brain Tumors ◽  
Neurological Diseases ◽  
Hsv 1

scholarly journals HSV-1-Based Vectors for Gene Therapy of Neurological Diseases and Brain Tumors: Part II. Vector Systems and Applications

Neoplasia ◽  
1999 ◽  
Vol 1 (5) ◽  
pp. 402-416 ◽  
Author(s):  
Andreas Jacobs ◽  
Xandra O. Breakefield ◽  
Cornel Fraefel
Keyword(s):  
Gene Therapy ◽  
Brain Tumors ◽  
Neurological Diseases ◽  
Vector Systems ◽  
Hsv 1

Thymidine kinase-mediated killing of rat brain tumors

1993 ◽  
Vol 79 (5) ◽  
pp. 729-735 ◽  
Author(s):  
David Barba ◽  
Joseph Hardin ◽  
Jasodhara Ray ◽  
Fred H. Gage
Keyword(s):  
Gene Therapy ◽  
Brain Tumors ◽  
Tumor Cells ◽  
Wild Type ◽  
Cns Disorders ◽  
Content Type ◽  
Potential Applications ◽  
Ganciclovir Treatment ◽  
The Brain ◽  
Fine Print

✓ Gene therapy has many potential applications in central nervous system (CNS) disorders, including the selective killing of tumor cells in the brain. A rat brain tumor model was used to test the herpes simplex virus (HSV)-thymidine kinase (TK) gene for its ability to selectively kill C6 and 9L tumor cells in the brain following systemic administration of the nucleoside analog ganciclovir. The HSV-TK gene was introduced in vitro into tumor cells (C6-TK and 9L-TK), then these modified tumor cells were evaluated for their sensitivity to cell killing by ganciclovir. In a dose-response assay, both C6-TK and 9L-TK cells were 100 times more sensitive to killing by ganciclovir (median lethal dose: C6-TK, 0.1 µg ganciclovir/ml; C6, 5.0 µg ganciclovir/ml) than unmodified wild-type tumor cells or cultured fibroblasts. In vivo studies confirmed the ability of intraperitoneal ganciclovir administration to kill established brain tumors in rats as quantified by both stereological assessment of brain tumor volumes and studies of animal survival over 90 days. Rats with brain tumors established by intracerebral injection of wild-type or HSV-TK modified tumor cells or by a combination of wild-type and HSV-TK-modified cells were studied with and without ganciclovir treatments. Stereological methods determined that ganciclovir treatment eliminated tumors composed of HSV-TK-modified cells while control tumors grew as expected (p < 0.001). In survival studies, all 10 rats with 9L-TK tumors treated with ganciclovir survived 90 days while all untreated rats died within 25 days. Curiously, tumors composed of combinations of 9L and 9L-TK cells could be eliminated by ganciclovir treatments even when only one-half of the tumor cells carried the HSV-TK gene. While not completely understood, this additional tumor cell killing appears to be both tumor selective and local in nature. It is concluded that HSV-TK gene therapy with ganciclovir treatment does selectively kill tumor cells in the brain and has many potential applications in CNS disorders, including the treatment of cancer.

scholarly journals Efficient and Selective Gene Transfer into Primary Human Brain Tumors by Using Single-Chain Antibody-Targeted Adenoviral Vectors with Native Tropism Abolished

2002 ◽  
Vol 76 (6) ◽  
pp. 2753-2762 ◽  
Author(s):  
Victor W. van Beusechem ◽  
Jacques Grill ◽  
D. C. Jeroen Mastenbroek ◽  
Thomas J. Wickham ◽  
Peter W. Roelvink ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Gene Transfer ◽  
Brain Tumors ◽  
Human Brain ◽  
Cancer Gene Therapy ◽  
Adenoviral Vectors ◽  
Receptor Expression ◽  
Normal Brain ◽  
Cancer Gene ◽  
Single Chain

ABSTRACT The application of adenoviral vectors in cancer gene therapy is hampered by low receptor expression on tumor cells and high receptor expression on normal epithelial cells. Targeting adenoviral vectors toward tumor cells may improve cancer gene therapy procedures by providing augmented tumor transduction and decreased toxicity to normal tissues. Targeting requires both the complete abolition of native tropism and the addition of a new specific binding ligand onto the viral capsid. Here we accomplished this by using doubly ablated adenoviral vectors, lacking coxsackievirus-adenovirus receptor and αv integrin binding capacities, together with bispecific single-chain antibodies targeted toward human epidermal growth factor receptor (EGFR) or the epithelial cell adhesion molecule. These vectors efficiently and selectively targeted both alternative receptors on the surface of human cancer cells. Targeted doubly ablated adenoviral vectors were also very efficient and specific with primary human tumor specimens. With primary glioma cell cultures, EGFR targeting augmented the median gene transfer efficiency of doubly ablated adenoviral vectors 123-fold. Moreover, EGFR-targeted doubly ablated vectors were selective for human brain tumors versus the surrounding normal brain tissue. They transduced organotypic glioma and meningioma spheroids with efficiencies similar to those of native adenoviral vectors, while exhibiting greater-than-10-fold-reduced background levels on normal brain explants from the same patients. As a result, EGFR-targeted doubly ablated adenoviral vectors had a 5- to 38-fold-improved tumor-to-normal brain targeting index compared to native vectors. Hence, single-chain targeted doubly ablated adenoviral vectors are promising tools for cancer gene therapy. They should provide an improved therapeutic index with efficient tumor transduction and effective protection of normal tissue.

Cytokine-Based Gene Therapy for Brain Tumors

1998 ◽  
pp. 231-294 ◽  
Author(s):  
John H. Sampson ◽  
Darell D. Bigner ◽  
Glenn Dranoff
Keyword(s):  
Gene Therapy ◽  
Brain Tumors

HERPES SIMPLEX VIRUS TYPE-1 (HSV-1) MUTANTS FOR THE TREATMENT OF CHILDHOOD BRAIN TUMORS

1996 ◽  
Vol 55 (5) ◽  
pp. 623
Author(s):  
T. M. Lasner ◽  
S. Kesari ◽  
S. M. Brown ◽  
N. W. Fraser ◽  
J. Q. Trojanowski
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Brain Tumors ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Childhood Brain Tumors ◽  
Simplex Virus ◽  
Hsv 1

Gene Therapy for Brain Tumors

2018 ◽  
pp. 243-262
Author(s):  
Kenneth W. Culver ◽  
John Van Gilder ◽  
Thomas Carlstrom ◽  
Michael Prados ◽  
Charles J. Link
Keyword(s):  
Gene Therapy ◽  
Brain Tumors

scholarly journals Aptamer Applications in Neuroscience

2021 ◽  
Author(s):  
Meric Ozturk ◽  
Marit Nilsen-Hamilton ◽  
Muslum Ilgu
Keyword(s):  
Multiple Sclerosis ◽  
Amyotrophic Lateral Sclerosis ◽  
Nucleic Acid ◽  
Brain Tumors ◽  
Neurological Disorders ◽  
Neurological Diseases ◽  
Treatment Options ◽  
Health Community ◽  
Theranostic Applications ◽  
Lateral Sclerosis

Being the predominant cause of disability, neurological diseases have received much attention from the global health community. Over a billion people suffer from one of the following neurological disorders: dementia, epilepsy, stroke, migraine, meningitis, Alzheimer's disease, Parkinson&rsquo;s disease, multiple sclerosis, amyotrophic lateral sclerosis, Huntington&rsquo;s disease, prion dis-ease, or brain tumors. Diagnosis and treatment options are limited for many of these diseases. Aptamers, being small and non-immunogenic nucleic acid molecules that are easy to chemically modify, offer potential diagnostic and theranostic applications to meet these needs. This review covers pioneer studies to apply aptamers, which show promise for future diagnostics and treatments of neurological disorders that pose increasingly dire worldwide health challenges.

scholarly journals Aptamer Applications in Neuroscience

2021 ◽  
Vol 14 (12) ◽  
pp. 1260
Author(s):  
Meric Ozturk ◽  
Marit Nilsen-Hamilton ◽  
Muslum Ilgu
Keyword(s):  
Multiple Sclerosis ◽  
Amyotrophic Lateral Sclerosis ◽  
Nucleic Acid ◽  
Brain Tumors ◽  
Global Health ◽  
Neurological Disorders ◽  
Neurological Diseases ◽  
Treatment Options ◽  
Health Community ◽  
Lateral Sclerosis

Being the predominant cause of disability, neurological diseases have received much attention from the global health community. Over a billion people suffer from one of the following neurological disorders: dementia, epilepsy, stroke, migraine, meningitis, Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, amyotrophic lateral sclerosis, Huntington’s disease, prion disease, or brain tumors. The diagnosis and treatment options are limited for many of these diseases. Aptamers, being small and non-immunogenic nucleic acid molecules that are easy to chemically modify, offer potential diagnostic and theragnostic applications to meet these needs. This review covers pioneering studies in applying aptamers, which shows promise for future diagnostics and treatments of neurological disorders that pose increasingly dire worldwide health challenges.

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