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Seek and destroy: Targeted adeno-associated viruses for gene delivery to hepatocellular carcinoma

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journal contribution
posted on 2022-09-06, 04:20 authored by B Dhungel, A Jayachandran, Christopher LaytonChristopher Layton, Jason SteelJason Steel
Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer with high incidence globally. Increasing mortality and morbidity rates combined with limited treatment options available for advanced HCC press for novel and effective treatment modalities. Gene therapy represents one of the most promising therapeutic options. With the recent approval of herpes simplex virus for advanced melanoma, the field of gene therapy has received a major boost. Adeno-associated virus (AAV) is among the most widely used and effective viral vectors today with safety and efficacy demonstrated in a number of human clinical trials. This review identifies the obstacles for effective AAV based gene delivery to HCC which primarily include host immune responses and off-target effects. These drawbacks could be more pronounced for HCC because of the underlying liver dysfunction in most of the patients. We discuss approaches that could be adopted to tackle these shortcomings and manufacture HCC-targeted vectors. The combination of transductional targeting by modifying the vector capsid and transcriptional targeting using HCC-specific promoters has the potential to produce vectors which can specifically seek HCC and deliver therapeutic gene without significant side effects. Finally, the identification of novel HCC-specific ligands and promoters should facilitate and expedite this process.

History

Volume

24

Issue

1

Start Page

289

End Page

299

Number of Pages

11

eISSN

1521-0464

ISSN

1071-7544

Location

England

Publisher

Taylor & Francis

Publisher License

CC BY

Additional Rights

CC BY 4.0

Language

eng

Peer Reviewed

  • Yes

Open Access

  • Yes

Acceptance Date

2016-10-10

Era Eligible

  • Yes

Medium

Print

Journal

Drug Delivery