AAV Vector-Mediated Liver Gene Therapy and Its Implementation for Hemophilia

2016 ◽  
pp. 59-73 ◽  
Author(s):  
Hiroaki Mizukami ◽  
Jun Mimuro ◽  
Tsukasa Ohmori ◽  
Yoichi Sakata ◽  
Keiya Ozawa
Keyword(s):  
Gene Therapy ◽  
Aav Vector ◽  
Liver Gene

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.

Liver Gene Therapy: Will Gene Therapy Deliver to the Liver Patient?

2008 ◽  
pp. 441-449
Author(s):  
N. Levicar ◽  
L. Jiao ◽  
Ph. Bachellier ◽  
D. Zaharoulis ◽  
D. Jaeck ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Liver Gene

scholarly journals Hemophilia gene therapy: ushering in a new treatment paradigm?

Hematology ◽  
2021 ◽  
Vol 2021 (1) ◽  
pp. 226-233
Author(s):  
Lindsey A. George
Keyword(s):  
Clinical Trial ◽  
Gene Therapy ◽  
Clinical Trials ◽  
Hemophilia A ◽  
Full Potential ◽  
Proof Of Concept ◽  
Aav Vector ◽  
Treatment Paradigm ◽  
Clinical Trial Enrollment ◽  
New Treatment

Abstract After 3 decades of clinical trials, repeated proof-of-concept success has now been demonstrated in hemophilia A and B gene therapy. Current clinical hemophilia gene therapy efforts are largely focused on the use of systemically administered recombinant adeno-associated viral (rAAV) vectors for F8 or F9 gene addition. With multiple ongoing trials, including licensing studies in hemophilia A and B, many are cautiously optimistic that the first AAV vectors will obtain regulatory approval within approximately 1 year. While supported optimism suggests that the goal of gene therapy to alter the paradigm of hemophilia care may soon be realized, a number of outstanding questions have emerged from clinical trial that are in need of answers to harness the full potential of gene therapy for hemophilia patients. This article reviews the use of AAV vector gene addition approaches for hemophilia A and B, focusing specifically on information to review in the process of obtaining informed consent for hemophilia patients prior to clinical trial enrollment or administering a licensed AAV vector.

scholarly journals Advances in AAV Vector Development for Gene Therapy in the Retina

2014 ◽  
pp. 687-693 ◽  
Author(s):  
Timothy P. Day ◽  
Leah C. Byrne ◽  
David V. Schaffer ◽  
John G. Flannery
Keyword(s):  
Gene Therapy ◽  
Aav Vector

scholarly journals Liver Gene Therapy: Reliable and Durable?

2019 ◽  
Vol 27 (11) ◽  
pp. 1863-1864 ◽  
Author(s):  
Roland W. Herzog ◽  
Glenn F. Pierce
Keyword(s):  
Gene Therapy ◽  
Liver Gene

scholarly journals Helper-dependent adenoviral liver gene therapy protects against induced attacks and corrects protein folding stress in acute intermittent porphyria mice

2013 ◽  
Vol 22 (14) ◽  
pp. 2929-2940 ◽  
Author(s):  
Carmen Unzu ◽  
Ana Sampedro ◽  
Itsaso Mauleón ◽  
Manuela González-Aparicio ◽  
Rafael Enríquez de Salamanca ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Protein Folding ◽  
Acute Intermittent Porphyria ◽  
Liver Gene
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