Calcium gluconate in phosphate buffered saline increases gene delivery with adenovirus type 5.

<h4>Background</h4>Adenoviruses are attractive vectors for gene therapy because of their stability in vivo and the possibility of production at high titers. Despite exciting preclinical data with various approaches, there are only a few examples of clear efficacy in clinical trials. Effe...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Marko T Ahonen, Iulia Diaconu, Sari Pesonen, Anna Kanerva, Marc Baumann, Suvi T Parviainen, Brad Spiller, Vincenzo Cerullo, Akseli Hemminki
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/fa46758582e148668c18afbb2e95243f
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:fa46758582e148668c18afbb2e95243f
record_format	dspace
spelling	oai:doaj.org-article:fa46758582e148668c18afbb2e95243f2021-11-18T07:03:47ZCalcium gluconate in phosphate buffered saline increases gene delivery with adenovirus type 5.1932-620310.1371/journal.pone.0013103https://doaj.org/article/fa46758582e148668c18afbb2e95243f2010-09-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20927353/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Adenoviruses are attractive vectors for gene therapy because of their stability in vivo and the possibility of production at high titers. Despite exciting preclinical data with various approaches, there are only a few examples of clear efficacy in clinical trials. Effective gene delivery to target cells remains the key variable determining efficacy and thus enhanced transduction methods are important.<h4>Methods/results</h4>We found that heated serum could enhance adenovirus 5 mediated gene delivery up to twentyfold. A new protein-level interaction was found between fiber knob and serum transthyretin, but this was not responsible for the observed effect. Instead, we found that heating caused the calcium and phosphate present in the serum mix to precipitate, and this was responsible for enhanced gene delivery. This finding could have relevance for designing preclinical experiments with adenoviruses, since calcium and phosphate are present in many solutions. To translate this into an approach potentially testable in patients, we used calcium gluconate in phosphate buffered saline, both of which are clinically approved, to increase adenoviral gene transfer up to 300-fold in vitro. Gene transfer was increased with or without heating and in a manner independent from the coxsackie-adenovirus receptor. In vivo, in mouse studies, gene delivery was increased 2-, 110-, 12- and 13-fold to tumors, lungs, heart and liver and did not result in increased pro-inflammatory cytokine induction. Antitumor efficacy of a replication competent virus was also increased significantly.<h4>Conclusion</h4>In summary, adenoviral gene transfer and antitumor efficacy can be enhanced by calcium gluconate in phosphate buffered saline.Marko T AhonenIulia DiaconuSari PesonenAnna KanervaMarc BaumannSuvi T ParviainenBrad SpillerVincenzo CerulloAkseli HemminkiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 9 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Marko T Ahonen Iulia Diaconu Sari Pesonen Anna Kanerva Marc Baumann Suvi T Parviainen Brad Spiller Vincenzo Cerullo Akseli Hemminki Calcium gluconate in phosphate buffered saline increases gene delivery with adenovirus type 5.
description	<h4>Background</h4>Adenoviruses are attractive vectors for gene therapy because of their stability in vivo and the possibility of production at high titers. Despite exciting preclinical data with various approaches, there are only a few examples of clear efficacy in clinical trials. Effective gene delivery to target cells remains the key variable determining efficacy and thus enhanced transduction methods are important.<h4>Methods/results</h4>We found that heated serum could enhance adenovirus 5 mediated gene delivery up to twentyfold. A new protein-level interaction was found between fiber knob and serum transthyretin, but this was not responsible for the observed effect. Instead, we found that heating caused the calcium and phosphate present in the serum mix to precipitate, and this was responsible for enhanced gene delivery. This finding could have relevance for designing preclinical experiments with adenoviruses, since calcium and phosphate are present in many solutions. To translate this into an approach potentially testable in patients, we used calcium gluconate in phosphate buffered saline, both of which are clinically approved, to increase adenoviral gene transfer up to 300-fold in vitro. Gene transfer was increased with or without heating and in a manner independent from the coxsackie-adenovirus receptor. In vivo, in mouse studies, gene delivery was increased 2-, 110-, 12- and 13-fold to tumors, lungs, heart and liver and did not result in increased pro-inflammatory cytokine induction. Antitumor efficacy of a replication competent virus was also increased significantly.<h4>Conclusion</h4>In summary, adenoviral gene transfer and antitumor efficacy can be enhanced by calcium gluconate in phosphate buffered saline.
format	article
author	Marko T Ahonen Iulia Diaconu Sari Pesonen Anna Kanerva Marc Baumann Suvi T Parviainen Brad Spiller Vincenzo Cerullo Akseli Hemminki
author_facet	Marko T Ahonen Iulia Diaconu Sari Pesonen Anna Kanerva Marc Baumann Suvi T Parviainen Brad Spiller Vincenzo Cerullo Akseli Hemminki
author_sort	Marko T Ahonen
title	Calcium gluconate in phosphate buffered saline increases gene delivery with adenovirus type 5.
title_short	Calcium gluconate in phosphate buffered saline increases gene delivery with adenovirus type 5.
title_full	Calcium gluconate in phosphate buffered saline increases gene delivery with adenovirus type 5.
title_fullStr	Calcium gluconate in phosphate buffered saline increases gene delivery with adenovirus type 5.
title_full_unstemmed	Calcium gluconate in phosphate buffered saline increases gene delivery with adenovirus type 5.
title_sort	calcium gluconate in phosphate buffered saline increases gene delivery with adenovirus type 5.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/fa46758582e148668c18afbb2e95243f
work_keys_str_mv	AT markotahonen calciumgluconateinphosphatebufferedsalineincreasesgenedeliverywithadenovirustype5 AT iuliadiaconu calciumgluconateinphosphatebufferedsalineincreasesgenedeliverywithadenovirustype5 AT saripesonen calciumgluconateinphosphatebufferedsalineincreasesgenedeliverywithadenovirustype5 AT annakanerva calciumgluconateinphosphatebufferedsalineincreasesgenedeliverywithadenovirustype5 AT marcbaumann calciumgluconateinphosphatebufferedsalineincreasesgenedeliverywithadenovirustype5 AT suvitparviainen calciumgluconateinphosphatebufferedsalineincreasesgenedeliverywithadenovirustype5 AT bradspiller calciumgluconateinphosphatebufferedsalineincreasesgenedeliverywithadenovirustype5 AT vincenzocerullo calciumgluconateinphosphatebufferedsalineincreasesgenedeliverywithadenovirustype5 AT akselihemminki calciumgluconateinphosphatebufferedsalineincreasesgenedeliverywithadenovirustype5
_version_	1718424015754756096

Calcium gluconate in phosphate buffered saline increases gene delivery with adenovirus type 5.

Ejemplares similares