Bioluminescence imaging reveals a significant role for complement in liver transduction following intravenous delivery of adenovirus

K. R. Zinn; A. J. Szalai; A. Stargel; V. Krasnykh; T. R. Chaudhuri

doi:10.1038/sj.gt.3302331

Bioluminescence imaging reveals a significant role for complement in liver transduction following intravenous delivery of adenovirus

K. R. Zinn, A. J. Szalai, A. Stargel, V. Krasnykh, T. R. Chaudhuri

Cancer Systems Imaging

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

39 Scopus citations

Abstract

The effect of complement on transgene expression was evaluated in vivo and in vitro using mice lacking complement components. Complement component 3 (C3) deficient mice (C3^-/-) and appropriate wild-type controls were intravenously injected with a replication incompetent, luciferase-expressing normal Ad5 (Ad5Luc1), or fibritin-fiber Ad5 (Ad5FFLuc1). Repeated, noninvasive bioluminescence imaging was conducted over 35 days. Our data show for the first time that C3 facilitates both short- and long-term hepatic expression of luciferase following systemic delivery. C3^-/- mice showed significantly less (P < 0.05) luciferase expression in their liver than treatment-matched wild-type mice when 2.3 × 10⁹ (Ad5Luc1) and 4.0 × 10⁹ (Ad5Luc1 or Ad5FFLuc1) viral particles (v.p.) were infused. The maximal difference in luciferase activity between C3^-/- and wild-type mice was 99-fold difference at 3 days for the 2.3 × 10⁹ v.p. dose (Ad5Luc1), 35-fold at 13 days for the 4.0 × 10⁹ v.p. dose (Ad5Luc1), and 22-fold at 13 days for the 4.0 × 10⁹ v.p. dose (Ad5FFLuc1). Preincubation of Ad5Luc1 with wild-type, C1q^-/-, or factor B (FB) deficient mouse sera for 5 min significantly (P < 0.05) increased transduction of mouse liver cells, as compared to preincubation with C3^-/- sera or PBS. These results suggest the classical or alternate complement pathway enhances Ad5-mediated liver transduction.

Original language	English (US)
Pages (from-to)	1482-1486
Number of pages	5
Journal	Gene Therapy
Volume	11
Issue number	19
DOIs	https://doi.org/10.1038/sj.gt.3302331
State	Published - Oct 2004

Keywords

Adenovirus
Complement
Gene therapy
Inflammation
Innate immunity
Luciferase

ASJC Scopus subject areas

Molecular Medicine
Molecular Biology
Genetics

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10.1038/sj.gt.3302331

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@article{00e7c3ccdf0f494b9857dc2b5a5d40b2,

title = "Bioluminescence imaging reveals a significant role for complement in liver transduction following intravenous delivery of adenovirus",

abstract = "The effect of complement on transgene expression was evaluated in vivo and in vitro using mice lacking complement components. Complement component 3 (C3) deficient mice (C3-/-) and appropriate wild-type controls were intravenously injected with a replication incompetent, luciferase-expressing normal Ad5 (Ad5Luc1), or fibritin-fiber Ad5 (Ad5FFLuc1). Repeated, noninvasive bioluminescence imaging was conducted over 35 days. Our data show for the first time that C3 facilitates both short- and long-term hepatic expression of luciferase following systemic delivery. C3-/- mice showed significantly less (P < 0.05) luciferase expression in their liver than treatment-matched wild-type mice when 2.3 × 109 (Ad5Luc1) and 4.0 × 109 (Ad5Luc1 or Ad5FFLuc1) viral particles (v.p.) were infused. The maximal difference in luciferase activity between C3-/- and wild-type mice was 99-fold difference at 3 days for the 2.3 × 109 v.p. dose (Ad5Luc1), 35-fold at 13 days for the 4.0 × 109 v.p. dose (Ad5Luc1), and 22-fold at 13 days for the 4.0 × 109 v.p. dose (Ad5FFLuc1). Preincubation of Ad5Luc1 with wild-type, C1q-/-, or factor B (FB) deficient mouse sera for 5 min significantly (P < 0.05) increased transduction of mouse liver cells, as compared to preincubation with C3-/- sera or PBS. These results suggest the classical or alternate complement pathway enhances Ad5-mediated liver transduction.",

keywords = "Adenovirus, Complement, Gene therapy, Inflammation, Innate immunity, Luciferase",

author = "Zinn, {K. R.} and Szalai, {A. J.} and A. Stargel and V. Krasnykh and Chaudhuri, {T. R.}",

note = "Funding Information: Research support was derived from NIH Grant Numbers CA80104 and 5P50CA089019, as well as DAMD17-02-01-0266. We thank Glorisa Reason for assistance with liver assays.",

year = "2004",

month = oct,

doi = "10.1038/sj.gt.3302331",

language = "English (US)",

volume = "11",

pages = "1482--1486",

journal = "Gene Therapy",

issn = "0969-7128",

publisher = "Nature Publishing Group",

number = "19",

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TY - JOUR

T1 - Bioluminescence imaging reveals a significant role for complement in liver transduction following intravenous delivery of adenovirus

AU - Zinn, K. R.

AU - Szalai, A. J.

AU - Stargel, A.

AU - Krasnykh, V.

AU - Chaudhuri, T. R.

N1 - Funding Information: Research support was derived from NIH Grant Numbers CA80104 and 5P50CA089019, as well as DAMD17-02-01-0266. We thank Glorisa Reason for assistance with liver assays.

PY - 2004/10

Y1 - 2004/10

N2 - The effect of complement on transgene expression was evaluated in vivo and in vitro using mice lacking complement components. Complement component 3 (C3) deficient mice (C3-/-) and appropriate wild-type controls were intravenously injected with a replication incompetent, luciferase-expressing normal Ad5 (Ad5Luc1), or fibritin-fiber Ad5 (Ad5FFLuc1). Repeated, noninvasive bioluminescence imaging was conducted over 35 days. Our data show for the first time that C3 facilitates both short- and long-term hepatic expression of luciferase following systemic delivery. C3-/- mice showed significantly less (P < 0.05) luciferase expression in their liver than treatment-matched wild-type mice when 2.3 × 109 (Ad5Luc1) and 4.0 × 109 (Ad5Luc1 or Ad5FFLuc1) viral particles (v.p.) were infused. The maximal difference in luciferase activity between C3-/- and wild-type mice was 99-fold difference at 3 days for the 2.3 × 109 v.p. dose (Ad5Luc1), 35-fold at 13 days for the 4.0 × 109 v.p. dose (Ad5Luc1), and 22-fold at 13 days for the 4.0 × 109 v.p. dose (Ad5FFLuc1). Preincubation of Ad5Luc1 with wild-type, C1q-/-, or factor B (FB) deficient mouse sera for 5 min significantly (P < 0.05) increased transduction of mouse liver cells, as compared to preincubation with C3-/- sera or PBS. These results suggest the classical or alternate complement pathway enhances Ad5-mediated liver transduction.

AB - The effect of complement on transgene expression was evaluated in vivo and in vitro using mice lacking complement components. Complement component 3 (C3) deficient mice (C3-/-) and appropriate wild-type controls were intravenously injected with a replication incompetent, luciferase-expressing normal Ad5 (Ad5Luc1), or fibritin-fiber Ad5 (Ad5FFLuc1). Repeated, noninvasive bioluminescence imaging was conducted over 35 days. Our data show for the first time that C3 facilitates both short- and long-term hepatic expression of luciferase following systemic delivery. C3-/- mice showed significantly less (P < 0.05) luciferase expression in their liver than treatment-matched wild-type mice when 2.3 × 109 (Ad5Luc1) and 4.0 × 109 (Ad5Luc1 or Ad5FFLuc1) viral particles (v.p.) were infused. The maximal difference in luciferase activity between C3-/- and wild-type mice was 99-fold difference at 3 days for the 2.3 × 109 v.p. dose (Ad5Luc1), 35-fold at 13 days for the 4.0 × 109 v.p. dose (Ad5Luc1), and 22-fold at 13 days for the 4.0 × 109 v.p. dose (Ad5FFLuc1). Preincubation of Ad5Luc1 with wild-type, C1q-/-, or factor B (FB) deficient mouse sera for 5 min significantly (P < 0.05) increased transduction of mouse liver cells, as compared to preincubation with C3-/- sera or PBS. These results suggest the classical or alternate complement pathway enhances Ad5-mediated liver transduction.

KW - Adenovirus

KW - Complement

KW - Gene therapy

KW - Inflammation

KW - Innate immunity

KW - Luciferase

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U2 - 10.1038/sj.gt.3302331

DO - 10.1038/sj.gt.3302331

M3 - Article

C2 - 15295616

AN - SCOPUS:5444224131

SN - 0969-7128

VL - 11

SP - 1482

EP - 1486

JO - Gene Therapy

JF - Gene Therapy

IS - 19

ER -

Bioluminescence imaging reveals a significant role for complement in liver transduction following intravenous delivery of adenovirus

Abstract

Keywords

ASJC Scopus subject areas

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