A transfection compound series based on a versatile Tris linkage

Cameron, Fiona; Moghaddam, Minoo J.; Bender, Veronika; Whittaker, Robert G.; Mott, Margaret R.; Lockett, Trevor

doi:10.1016/s0005-2736(98)00248-x

Cited by 48 publications

(39 citation statements)

References 29 publications

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“…pOAdV-3-based plasmids carrying the appropriately mutated gene were digested with I-SceI to release the linear full-length genomes (17). The DNA was then transfected into permissive ovine cells for virus rescue using cationic lipid CS087 (5). Viruses were propagated, purified by double-CsCl banding, and characterized as described previously (3).…”

Section: Methodsmentioning

confidence: 99%

Cryoelectron Microscopy Map of Atadenovirus Reveals Cross-Genus Structural Differences from Human Adenovirus

Pantelic

Lockett

Rothnagel

et al. 2008

J Virol

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A three-dimensional (3D) cryoelectron microscopy reconstruction of the prototype Atadenovirus (OAdV [an ovine adenovirus isolate]) showing information at a 10.6-Å resolution (0.5 Fourier shell correlation) was derived by single-particle analysis. This is the first 3D structure solved for any adenovirus that is not a Mastadenovirus, allowing cross-genus comparisons between structures and the assignment of genus-specific capsid proteins. Viable OAdV mutants that lacked the genus-specific LH3 and p32k proteins in purified virions were also generated. Negatively stained 3D reconstructions of these mutants were used to identify the location of protein LH3 and infer that of p32k within the capsid. The key finding was that LH3 is a critical protein that holds the outer capsid of the virus together. In its absence, the outer viral capsid is unstable. LH3 is located in the same position among the hexon subunits as its protein IX equivalent from mastadenoviruses but sits on top of the hexon trimers, forming prominent "knobs" on the virion surface that visually distinguish OAdV from other known AdVs. Electron density was also assigned to hexon and penton subunits and to proteins IIIa and VIII. There was good correspondence between OAdV density and human AdV hexon structures, which also validated the significant differences that were observed between the penton base protein structures.The Adenoviridae comprise a large family of non-enveloped, icosahedral, generally nonpathogenic viruses with a doublestranded DNA genome (ϳ26.1 to 45 kb) (9). Because of their wide host range, viruses such as human adenovirus type 5 (AdV5) have been developed as gene delivery vectors and applied in the clinic, especially for cancer, monogenic disorders, and vaccination (http://www.wiley.co.uk/genmed /clinical/). While some of these trials have reached phases II and III, there is still considerable room for improvement in vector technology. In particular, there is strong interest in developing vectors that are targeted to specific tissues for improved therapeutic effect (6, 11), and for this purpose, structural information on the virus particle and its constituent molecules is paramount.The family Adenoviridae comprises four genera (Mastadenovirus, Aviadenovirus, Siadenovirus, and Atadenovirus). Of these, the best studied are the mastadenoviruses, which include viruses from numerous mammalian species and all known human AdVs. In contrast, members of the avi-, si-, and atadenoviruses have been isolated from birds, although the latter also occur widely in mammalian and reptilian species (9, 38). The prototype Atadenovirus, an ovine isolate (serotype 7; OAdV), is the only member for which any significant biological studies have been undertaken. OAdV uses a different (unknown) receptor from AdV5 and infects, but does not replicate in, human cells (15). It has also been developed as a gene delivery vector (2) and has regulatory approval to enter a phase I clinical trial for prostate cancer in 2008.Representative genomes from all four genera have now...

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Section: Methodsmentioning

confidence: 99%

Cryoelectron Microscopy Map of Atadenovirus Reveals Cross-Genus Structural Differences from Human Adenovirus

Pantelic

Lockett

Rothnagel

et al. 2008

J Virol

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“…However, the transfection efficiencies of a number of mono-cationic lipids 15,[39][40][41][42][43][44][45][66][67][68]74,75 have been demonstrated to be superior to that of LipofectAmine. Although investigations delineating transfection efficiencies of either purely tri-lysinated cationic lipids 76,77 or exclusively mono-lysinated cationic lipids 15,[77][78][79] have been reported, systematic structure-activity investigations using a library of cationic lipids with increasing number of positively charged headgroups have hardly been undertaken. To this end, recently we have designed and synthesized a series of novel cationic lipids with mono-, di-, and tri-lysine head-groups and common hydrophobic anchors.…”

Section: B Influence Of Head-group Nature and Head-group Chargesmentioning

confidence: 99%

Cationic liposomes as non‐viral carriers of gene medicines: Resolved issues, open questions, and future promises

Karmali

Chaudhuri

2006

Medicinal Research Reviews

257

141

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The clinical success of gene therapy is critically dependent on the development of efficient and safe gene delivery reagents, popularly known as "transfection vectors." The transfection vectors commonly used in gene therapy are mainly of two types: viral and non-viral. The efficiencies of viral transfection vectors are, in general, superior to their non-viral counterparts. However, the myriads of potentially adverse immunogenic aftermaths associated with the use of viral vectors are increasingly making the non-viral gene delivery reagents as the vectors of choice. Among the existing arsenal of non-viral gene delivery reagents, the distinct advantages associated with the use of cationic transfection lipids include their: (a) robust manufacture; (b) ease in handling and preparation techniques; (c) ability to inject large lipid:DNA complexes; and (d) low immunogenic response. The present review highlights the major achievements in the area of designing efficacious cationic transfection lipids, some of the more recent advances in the field of cationic liposomes-mediated gene transfer and targeted gene delivery, some unresolved issues and challenges in liposomal gene delivery, and future promises of cationic liposomes as gene-carriers in non-viral gene therapy.

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“…Cells were harvested 48 h after transfection. An enzyme-linked immunosorbent assay (ELISA) kit (Roche) was used to quantify CAT expression, while the expression of b-galactosidase was assayed using the monosodium salt of chlorophenol red-b-D-galactopyranoside substrate (Roche) as described elsewhere (Cameron et al, 1999). Inter-experiment variations arising from differences in transfection efficiency were corrected by normalizing for b-galactosidase expression.…”

Section: Ecr-controlled Gene Expression In Mammalian Cellsmentioning

confidence: 99%