Current Status of the Clinical Development of Gene Therapy

The liver is a key organ for metabolism, protein synthesis, detoxification, and endocrine function, and among liver diseases, including hepatitis, cirrhosis, malignant tumors, and congenital disease, liver cancer is one of the leading causes of cancer-related deaths worldwide. Conventional therapeutic options such as embolization and chemotherapy are not effective against advanced-stage liver cancer; therefore, continuous efforts focus on the development of novel therapeutic options, including molecular targeted agents and gene therapy. In this review, we will summarize the progress toward the development of gene therapies for liver cancer, with an emphasis on recent clinical trials and preclinical studies.

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Current Status and Challenges Associated with CNS-Targeted Gene Delivery across the BBB

Pharmaceutics ◽

10.3390/pharmaceutics12121216 ◽

2020 ◽

Vol 12 (12) ◽

pp. 1216

Author(s):

Seigo Kimura ◽

Hideyoshi Harashima

Keyword(s):

Gene Therapy ◽

Gene Delivery ◽

Neurological Disorders ◽

Viral Vectors ◽

New Drugs ◽

Brain Targeting ◽

Current Status ◽

Great Promise ◽

Targeted Gene Delivery ◽

The Central Nervous System

The era of the aging society has arrived, and this is accompanied by an increase in the absolute numbers of patients with neurological disorders, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). Such neurological disorders are serious costly diseases that have a significant impact on society, both globally and socially. Gene therapy has great promise for the treatment of neurological disorders, but only a few gene therapy drugs are currently available. Delivery to the brain is the biggest hurdle in developing new drugs for the central nervous system (CNS) diseases and this is especially true in the case of gene delivery. Nanotechnologies such as viral and non-viral vectors allow efficient brain-targeted gene delivery systems to be created. The purpose of this review is to provide a comprehensive review of the current status of the development of successful drug delivery to the CNS for the treatment of CNS-related disorders especially by gene therapy. We mainly address three aspects of this situation: (1) blood-brain barrier (BBB) functions; (2) adeno-associated viral (AAV) vectors, currently the most advanced gene delivery vector; (3) non-viral brain targeting by non-invasive methods.

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Nanoparticle-based thymulin gene therapy therapeutically reverses key pathology of experimental allergic asthma

Science Advances ◽

10.1126/sciadv.aay7973 ◽

2020 ◽

Vol 6 (24) ◽

pp. eaay7973

Author(s):

Adriana L. da Silva ◽

Gisele P. de Oliveira ◽

Namho Kim ◽

Fernanda F. Cruz ◽

Jamil Z. Kitoko ◽

...

Keyword(s):

Gene Therapy ◽

Single Dose ◽

Allergic Asthma ◽

Clinical Development ◽

Chronic Asthma ◽

Pathologic Features ◽

Mucus Barrier ◽

Experimental Allergic Asthma ◽

Experimental Allergic ◽

Unique Ability

Despite long-standing efforts to enhance care for chronic asthma, symptomatic treatments remain the only option to manage this highly prevalent and debilitating disease. We demonstrate that key pathology of allergic asthma can be almost completely resolved in a therapeutic manner by inhaled gene therapy. After the disease was fully and stably established, we treated mice intratracheally with a single dose of thymulin-expressing plasmids delivered via nanoparticles engineered to have a unique ability to penetrate the airway mucus barrier. Twenty days after the treatment, we found that all key pathologic features found in the asthmatic lung, including chronic inflammation, pulmonary fibrosis, and mechanical dysregulation, were normalized. We conducted tissue- and cell-based analyses to confirm that the therapeutic intervention was mediated comprehensively by anti-inflammatory and antifibrotic effects of the therapy. We believe that our findings open a new avenue for clinical development of therapeutically effective gene therapy for chronic asthma.

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Pre-clinical Development of a Lentiviral Vector Expressing the Anti-sickling βAS3 Globin for Gene Therapy for Sickle Cell Disease

Molecular Therapy — Methods & Clinical Development ◽

10.1016/j.omtm.2018.10.014 ◽

2018 ◽

Vol 11 ◽

pp. 167-179 ◽

Cited By ~ 5

Author(s):

Valentina Poletti ◽

Fabrizia Urbinati ◽

Sabine Charrier ◽

Guillaume Corre ◽

Roger P. Hollis ◽

...

Keyword(s):

Gene Therapy ◽

Sickle Cell Disease ◽

Sickle Cell ◽

Lentiviral Vector ◽

Clinical Development ◽

Cell Disease

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Gene therapy for neovascular age-related macular degeneration: rationale, clinical trials and future directions

British Journal of Ophthalmology ◽

10.1136/bjophthalmol-2020-316195 ◽

2020 ◽

pp. bjophthalmol-2020-316195 ◽

Cited By ~ 1

Author(s):

Thales Antonio Cabral de Guimaraes ◽

Michalis Georgiou ◽

James W B Bainbridge ◽

Michel Michaelides

Keyword(s):

Gene Therapy ◽

Clinical Trials ◽

Macular Degeneration ◽

Age Related Macular Degeneration ◽

Current Status ◽

Routes Of Administration ◽

Age Related ◽

Potential Safety ◽

Early Phase Clinical Trials ◽

Endothelial Growth Factor

Age-related macular degeneration (AMD) is one of the leading causes of irreversible blindness in the developed world. Antivascular endothelial growth factor therapy has transformed the management and outcome of neovascular AMD (nAMD), although the need for repeated intravitreal injections—even lifelong—and the related complications, high drug costs, frequent clinic visits and repeated imaging have resulted in an enormous burden both to healthcare systems and patients. The application of gene therapy approaches for sustained delivery of a range of antiangiogenic proteins has the promise of helping to address these aforementioned challenges. A number of early phase clinical trials of gene therapy in nAMD have provided encouraging results, with many more ongoing or anticipated. There remain significant areas of controversy, including regarding the optimal treatment targets, routes of administration and potential safety concerns. In this review we aim to provide an update of the current status of gene therapy for nAMD and briefly discuss future prospects.

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