scholarly journals Progresses towards safe and efficient gene therapy vectors

Oncotarget ◽  
2015 ◽  
Vol 6 (31) ◽  
pp. 30675-30703 ◽  
Author(s):  
Sergiu Chira ◽  
Carlo S. Jackson ◽  
Iulian Oprea ◽  
Ferhat Ozturk ◽  
Michael S. Pepper ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Efficient Gene ◽  
Gene Therapy Vectors

scholarly journals Impact of Medium-Sized Extracellular Vesicles on the Transduction Efficiency of Adeno-Associated Viruses in Neuronal and Primary Astrocyte Cell Cultures

2021 ◽  
Vol 22 (8) ◽  
pp. 4221
Author(s):  
Orsolya Tünde Kovács ◽  
Eszter Soltész-Katona ◽  
Nikolett Marton ◽  
Eszter Baricza ◽  
László Hunyady ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Extracellular Vesicles ◽  
Neutralizing Antibodies ◽  
Phospholipid Bilayer ◽  
Transduction Efficiency ◽  
Target Cells ◽  
Primary Astrocyte ◽  
Efficient Gene ◽  
Gene Therapy Vectors

(1) Adeno-associated viruses (AAV) are safe and efficient gene therapy vectors with promising results in the treatment of several diseases. Extracellular vesicles (EV) are phospholipid bilayer-surrounded structures carrying several types of lipids, proteins, and nucleic acids with the ability to cross biological barriers. EV-associated AAVs might serve as new and efficient gene therapy vectors considering that they carry the benefits of both AAVs and EVs. (2) We tested vesicle-associated AAVs and vesicles mixed with AAVs on two major cell types of the central nervous system: a neural cell line (N2A) and primary astrocyte cells. (3) In contrast to previously published in vivo observations, the extracellular vesicle packaging did not improve but, in the case of primary astrocyte cells, even inhibited the infection capacity of the AAV particles. The observed effect was not due to the inhibitory effects of the vesicles themselves, since mixing the AAVs with extracellular vesicles did not change the effectiveness. (4) Our results suggest that improvement of the in vivo efficacy of the EV-associated AAV particles is not due to the enhanced interaction between the AAV and the target cells, but most likely to the improved delivery of the AAVs through tissue barriers and to the shielding of AAVs from neutralizing antibodies.

Genetic Engineering of AAV Capsid Gene for Gene Therapy Application

2020 ◽  
Vol 20 (5) ◽  
pp. 321-332
Author(s):  
Yunbo Liu ◽  
Xu Zhang ◽  
Lin Yang
Keyword(s):  
Gene Therapy ◽  
Neutralizing Antibodies ◽  
Human Subjects ◽  
Genetic Diseases ◽  
Capsid Gene ◽  
Human Populations ◽  
Stable Gene ◽  
Efficient Gene ◽  
Gene Therapy Application

Adeno-associated virus (AAV) is a promising vector for in vivo gene therapy because of its excellent safety profile and ability to mediate stable gene expression in human subjects. However, there are still numerous challenges that need to be resolved before this gene delivery vehicle is used in clinical applications, such as the inability of AAV to effectively target specific tissues, preexisting neutralizing antibodies in human populations, and a limited AAV packaging capacity. Over the past two decades, much genetic modification work has been performed with the AAV capsid gene, resulting in a large number of variants with modified characteristics, rendering AAV a versatile vector for more efficient gene therapy applications for different genetic diseases.

scholarly journals Quantitation of Trace Levels of DNA Released from Disrupted Adeno-Associated Virus Gene Therapy Vectors

2021 ◽  
Author(s):  
Jared S. Bee ◽  
Kristin O'Berry ◽  
Yu (Zoe) Zhang ◽  
Megan Kuhn Phillippi ◽  
Akanksha Kaushal ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Adeno Associated Virus ◽  
Virus Gene ◽  
Gene Therapy Vectors

A novel purification strategy for retrovirus gene therapy vectors using heparin affinity chromatography

2005 ◽  
Vol 90 (4) ◽  
pp. 391-404 ◽  
Author(s):  
Mar�a de las Mercedes Segura ◽  
Amine Kamen ◽  
Pierre Trudel ◽  
Alain Garnier
Keyword(s):  
Gene Therapy ◽  
Affinity Chromatography ◽  
Gene Therapy Vectors ◽  
Heparin Affinity

Efficient gene therapy based targeting system for the treatment of inoperable tumors

2012 ◽  
Vol 14 (4) ◽  
pp. 221-230 ◽  
Author(s):  
Thomas Wirth ◽  
Jere Tuomas Pikkarainen ◽  
Haritha Dhammika Samaranayake ◽  
Pauliina Lehtolainen-Dalkilic ◽  
Hanna Pirita Lesch ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Efficient Gene

scholarly journals Recognition of Virus Infection and Innate Host Responses to Viral Gene Therapy Vectors

2010 ◽  
Vol 18 (8) ◽  
pp. 1422-1429 ◽  
Author(s):  
Dmitry M Shayakhmetov ◽  
Nelson C Di Paolo ◽  
Karen L Mossman
Keyword(s):  
Gene Therapy ◽  
Virus Infection ◽  
Host Responses ◽  
Viral Gene ◽  
Viral Gene Therapy ◽  
Gene Therapy Vectors

AAV9 is considered the most efficient AAV serotype targeting blood-brain barriers. To enhance effective gene therapy for CNS illnesses, testing novel vectors with more efficient crossing capabilities is vital

2021 ◽  
Author(s):  
Moataz Dowaidar
Keyword(s):  
Gene Therapy ◽  
Intravenous Injection ◽  
Peripheral Circulation ◽  
Full Potential ◽  
Cns Diseases ◽  
Aav Vector ◽  
Early Clinical Trial ◽  
Blood Brain ◽  
Efficient Gene ◽  
Trial Outcomes

Although gene therapy for CNS diseases shows promise in cell and animal investigations, most human trials have failed to satisfy the requisite requirements. Finding novel techniques to boost the efficacy of gene therapy in treating CNS diseases is still crucial. A growing number of clinical trials have proved the efficacy and safety of using AAV vectors, making AAV vector research a gene therapy hotspot. However, due to the presence of the BBB, many siRNA and DNA with potential therapeutic value are difficult to transport from peripheral circulation to the brain using AAV vectors, limiting the clinical impact of gene therapy drugs in the CNS and posing a major challenge to the field of CNS gene therapy. In early studies, AAV9 was considered the most effective AAV serotype for getting through the blood-brain barrier and transduction to central nervous system cells following intravenous injection. Aavrh10 isolated from rhesus monkeys was equal to, if not superior to, AAV9. AAV-PHP.B, a newly built capsid, exhibits 40-fold greater efficacy than AAV9 in astrocyte and neuron transduction. AAV-PHP.eB, a modified AAV-PHP.B variety, was identified to retain PHP.B's AAV-capacity to transduce astrocytes while enhancing neuronal transduction. While the four serotypes AAV9, AAVrh10, AAV-PHP.B, and AAV-PHP.eB have been validated to penetrate mice's BBB following intravenous injection, the number of AAV vectors that can do so is low. Moreover, the manner in which AAV vectors penetrate the BBB remains unclear. To promote efficient gene therapy for CNS diseases, it is still important to test new vectors with more efficient crossing abilities and understand their crossing processes. In addition to technical challenges, AAV vectors in treating CNS diseases may be limited by cautious attitudes to innovative treatments. Continued advances in AAV vector research, together with early clinical trial outcomes, might help researchers achieve the full potential of AAV-based CNS disease therapies.

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