Cited by 386RNA Interference and Gene DeliveryNanoparticle-Based Drug DeliveryAdvanced Drug Delivery Systems

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Factors affecting blood clearance and in vivo distribution of polyelectrolyte complexes for gene delivery

Dash, P R, Read, M L, Barrett, L B, Wolfert, M A, Seymour, L W·1999·Gene Therapy

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Abstract

Self-assembling polycation/DNA complexes represent a promising synthetic vector for gene delivery. However, despite considerable versatility and transfectional activity in vitro, such materials are quickly eliminated from the bloodstream following intravenous injection (plasma alpha half-life typically less than 5 min). For targeted systemic delivery a more prolonged plasma circulation of the vector is essential. Here we have examined factors contributing to rapid elimination of poly(L-lysine) (pLL)/DNA complexes from the bloodstream, and implicate the binding of proteins to the polyelectrolyte complexes as a likely cause for their blood clearance. pLL/DNA complexes reisolated from serum associate with several proteins, depending on their net charge, although the major band on SDS-PAGE co-migrates with albumin. Serum albumin binds to pLL/DNA complexes in vitro, forming a ternary pLL/DNA/albumin complex which regains some ethidium bromide fluorescence and fails to move during agarose electrophoresis. Albumin also causes increased turbidity of complexes, and reduces their zeta potential to the same level (-16 mV) as is measured in serum. We propose that rapid plasma elimination of polycation/DNA complexes results from their binding serum albumin and other proteins, perhaps due to aggregation and phagocytic capture or accumulation of the ternary complexes in fine capillary beds.

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Authors: Dash, P. R., Read, M. L., Barrett, L. B., Wolfert, M. A., & Seymour, L. W.
Affiliations: University of Birmingham (GB)
ORCID: Dash, P R
Read, M L
Wolfert, M A
Seymour, L W
Venue: Gene Therapy
Publisher: Springer Science and Business Media LLC
Published: 1999-04-01
Volume: 6
Issue: 4
Pages: 643-650
ISSN: 0969-7128 (ISSN-L)
1476-5462
DOI: 10.1038/sj.gt.3300843
OpenAlex: W2031185644
Cited by: 386
References: 24
Citations by year: 2026: 4 · 2025: 3 · 2024: 1 · 2023: 7 · 2022: 3 · 2021: 5 · 2020: 9 · 2019: 14 · 2018: 11 · 2017: 13 · 2016: 14 · 2015: 11 · 2014: 22 · 2013: 31 · 2012: 22
FWCI: 4.94
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Gene Therapy (publishedVersion)
PubMed (publishedVersion)
University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
Funders: British Heart Foundation
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
Keywords: polyelectrolyte complexes, gene delivery, poly-L-lysine, DNA, blood clearance, serum albumin, protein binding, plasma half-life, zeta potential, complex aggregation, phagocytosis, intravenous injection, systemic drug delivery
MeSH terms: Albumins, Animals, DNA, Electrophoresis, Agar Gel, Female, Genetic Vectors, Metabolic Clearance Rate, Mice, Inbred BALB C, Polylysine, Protein Binding, Transfection, Genetic Therapy, Treatment Failure, Mice

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Factors affecting blood clearance and in vivo distribution of polyelectrolyte complexes for gene delivery

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