Development of novel adenoviral vectors to overcome challenges observed with HAdV-5-based constructs

Julio Alonso-Padilla; Tibor Papp; Gyozo L. Kaján; Mária Benko; Menzo Havenga; Angelique Lemckert; Balázs Harrach; Andrew H. Baker

doi:10.1038/mt.2015.194

Development of novel adenoviral vectors to overcome challenges observed with HAdV-5-based constructs

Julio Alonso-Padilla, Tibor Papp, Gyozo L. Kaján, Mária Benko, Menzo Havenga, Angelique Lemckert, Balázs Harrach, Andrew H. Baker^*

^*Corresponding author for this work

Research output: Contribution to journal › Literature review › peer-review

Abstract

Recombinant vectors based on human adenovirus serotype 5 (HAdV-5) have been extensively studied in preclinical models and clinical trials over the past two decades. However, the thorough understanding of the HAdV-5 interaction with human subjects has uncovered major concerns about its product applicability. High vector-associated toxicity and widespread preexisting immunity have been shown to significantly impede the effectiveness of HAdV-5-mediated gene transfer. It is therefore that the in-depth knowledge attained working on HAdV-5 is currently being used to develop alternative vectors. Here, we provide a comprehensive overview of data obtained in recent years disqualifying the HAdV-5 vector for systemic gene delivery as well as novel strategies being pursued to overcome the limitations observed with particular emphasis on the ongoing vectorization efforts to obtain vectors based on alternative serotypes.

Original language	English
Pages (from-to)	6-16
Number of pages	11
Journal	Molecular Therapy
Volume	24
Issue number	1
Early online date	19 Oct 2015
DOIs	https://doi.org/10.1038/mt.2015.194
Publication status	Published - 1 Feb 2016

Access to Document

10.1038/mt.2015.194

Baker AH Development of novel...
This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Final published version, 362 KBLicence: Creative Commons: Attribution (CC-BY)

Cite this

@article{7f686a4bdca54aabb4bd777a1f16210f,

title = "Development of novel adenoviral vectors to overcome challenges observed with HAdV-5-based constructs",

abstract = "Recombinant vectors based on human adenovirus serotype 5 (HAdV-5) have been extensively studied in preclinical models and clinical trials over the past two decades. However, the thorough understanding of the HAdV-5 interaction with human subjects has uncovered major concerns about its product applicability. High vector-associated toxicity and widespread preexisting immunity have been shown to significantly impede the effectiveness of HAdV-5-mediated gene transfer. It is therefore that the in-depth knowledge attained working on HAdV-5 is currently being used to develop alternative vectors. Here, we provide a comprehensive overview of data obtained in recent years disqualifying the HAdV-5 vector for systemic gene delivery as well as novel strategies being pursued to overcome the limitations observed with particular emphasis on the ongoing vectorization efforts to obtain vectors based on alternative serotypes.",

author = "Julio Alonso-Padilla and Tibor Papp and Kaj{\'a}n, {Gyozo L.} and M{\'a}ria Benko and Menzo Havenga and Angelique Lemckert and Bal{\'a}zs Harrach and Baker, {Andrew H.}",

year = "2016",

month = feb,

day = "1",

doi = "10.1038/mt.2015.194",

language = "English",

volume = "24",

pages = "6--16",

journal = "Molecular Therapy",

issn = "1525-0016",

publisher = "Cell Press",

number = "1",

}

TY - JOUR

T1 - Development of novel adenoviral vectors to overcome challenges observed with HAdV-5-based constructs

AU - Alonso-Padilla, Julio

AU - Papp, Tibor

AU - Kaján, Gyozo L.

AU - Benko, Mária

AU - Havenga, Menzo

AU - Lemckert, Angelique

AU - Harrach, Balázs

AU - Baker, Andrew H.

PY - 2016/2/1

Y1 - 2016/2/1

N2 - Recombinant vectors based on human adenovirus serotype 5 (HAdV-5) have been extensively studied in preclinical models and clinical trials over the past two decades. However, the thorough understanding of the HAdV-5 interaction with human subjects has uncovered major concerns about its product applicability. High vector-associated toxicity and widespread preexisting immunity have been shown to significantly impede the effectiveness of HAdV-5-mediated gene transfer. It is therefore that the in-depth knowledge attained working on HAdV-5 is currently being used to develop alternative vectors. Here, we provide a comprehensive overview of data obtained in recent years disqualifying the HAdV-5 vector for systemic gene delivery as well as novel strategies being pursued to overcome the limitations observed with particular emphasis on the ongoing vectorization efforts to obtain vectors based on alternative serotypes.

AB - Recombinant vectors based on human adenovirus serotype 5 (HAdV-5) have been extensively studied in preclinical models and clinical trials over the past two decades. However, the thorough understanding of the HAdV-5 interaction with human subjects has uncovered major concerns about its product applicability. High vector-associated toxicity and widespread preexisting immunity have been shown to significantly impede the effectiveness of HAdV-5-mediated gene transfer. It is therefore that the in-depth knowledge attained working on HAdV-5 is currently being used to develop alternative vectors. Here, we provide a comprehensive overview of data obtained in recent years disqualifying the HAdV-5 vector for systemic gene delivery as well as novel strategies being pursued to overcome the limitations observed with particular emphasis on the ongoing vectorization efforts to obtain vectors based on alternative serotypes.

UR - http://www.scopus.com/inward/record.url?scp=84957848237&partnerID=8YFLogxK

U2 - 10.1038/mt.2015.194

DO - 10.1038/mt.2015.194

M3 - Literature review

AN - SCOPUS:84957848237

SN - 1525-0016

VL - 24

SP - 6

EP - 16

JO - Molecular Therapy

JF - Molecular Therapy

IS - 1

ER -

Development of novel adenoviral vectors to overcome challenges observed with HAdV-5-based constructs

Abstract

Access to Document

Other files and links

Fingerprint

Cite this