Adding functional entities to plasmids

Svahn, Mathias G.; Lundin, Karin E.; Ge, Rongbin; Törnquist, Elisabeth; Simonson, Ernst; Oscarsson, Sven; Leijon, Mikael; Branden, Lars; Smith, C. I. Edvard

doi:10.1002/jgm.510

Cited by 23 publications

(12 citation statements)

References 28 publications

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“…By attaching small peptides or other molecules endowed with particular biological functions, like enhancing cell-specific uptake or intracellular transport to DNA, biologically active nano-complexes can be created. This method, which was named Bioplex formulation, utilizes sequence-specific hybridization of FEs via site-specific anchor molecules like PNA or LNA, and was initially used to increase nuclear transport of plasmid DNA (Branden et al 2001;Branden et al 1999;Svahn et al 2004a).…”

Section: Building Nano-complexes Via Nucleic Acid Hybridizationmentioning

confidence: 99%

Nanotechnology approaches for gene transfer

et al. 2009

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In both basic research as well as experimental gene therapy the need to transfer genetic material into a cell is of vital importance. The cellular compartment, which is the target for the genetic material, depends upon application. An siRNA that mediates silencing is preferably delivered to the cytosol while a transgene would need to end up in the nucleus for successful transcription to occur. Furthermore the ability to regulate gene expression has grown substantially since the discovery of RNA interference. In such diverse fields as medical research and agricultural pest control, the capability to alter the genetic output has been a useful tool for pushing the scientific frontiers. This review is focused on nanotechnological approaches to assemble optimised structures of nucleic acid derivatives to facilitate gene delivery as well as promoting down regulation of endogenous genes.

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Section: Building Nano-complexes Via Nucleic Acid Hybridizationmentioning

confidence: 99%

Nanotechnology approaches for gene transfer

et al. 2009

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“…proteins or other molecular entities. The PNA clamp, developed by C. I. Smith and coworkers (32)(33)(34) connects the entire construct to a selected region of the "pBluescript" plasmid, and binds via a sticky end to the ssDNA carrier strand. The latter 103 nucleotides (nt) carrier consists of a 15 nt long anchor for the attachment to the PNA clamp in addition to the four 22 nt long stretches for binding of the complementary DNA oligonucleotides of DNA-peptide and -protein conjugates (Figures 2 and 3).…”

Section: Sequence Design and Evaluation Of Self-assembled Nanostructuresmentioning

confidence: 99%

Semisynthetic DNA-protein conjugates for fabrication of nucleic acid based nanostructures

Rabe¹,

Feldkamp²,

Niemeyer³

2008

AIP Conference Proceedings

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We here report on the developments of semisynthetic DNA-protein conjugates and their assembly into multi-component nanostructures. We describe the improvement of the DNA sequences embedded in such nanostructures by computational and analytical methods. Moreover, we report on the exploration of novel DNA conjugates of streptavidin or redox proteins with improved properties for the assembly of nucleic acid based nanostructures.

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“…The Bioplex platform technology, reviewed by Brandén & Smith and Svahn et al [27,28], aims to combine the safety and conformity of non-viral gene transfer vectors with the efficacy of viral vectors. By adding Functional Entities (FEs) directly to the DNA we hope to create a stable and well-defined gene transfer system.…”

Section: Bioplexmentioning

confidence: 99%

“…PNAs are DNA mimics with interesting features that can be utilised in gene therapy, diagnostics and molecular biology applications [28][29][30]. PNAs are polyamide oligomers containing repeated N-(2-aminoethyl)glycin units with the nucleobases attached through methylenecarbonyl linkers that hybridise to DNA in a sequence specific manner [31,32].…”

Section: Peptide Nucleic Acidmentioning

confidence: 99%

Bioplex Technology: Novel Synthetic Gene Delivery Pharmaceutical Based on Peptides Anchored to Nucleic Acids

Simonson

Svahn

Törnquist

et al. 2005

CPD

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Non-viral gene delivery is an important approach in order to establish safe in vivo gene therapy in the clinic. Although viral vectors currently exhibit superior gene transfer efficacy, the safety aspect of viral gene delivery is a concern. In order to improve non-viral in vivo gene delivery we have designed a pharmaceutical platform called Bioplex (biological complex). The concept of Bioplex is to link functional entities via hybridising anchors, such as Peptide Nucleic Acids (PNA), directly to naked DNA. In order to promote delivery functional entities consisting of biologically active peptides or carbohydrates, are linked to the PNA anchor. The PNA acts as genetic glue and hybridises with DNA in a sequence specific manner. By using functional entities, which elicit receptor-mediated endocytosis, improved endosomal escape and enhance nuclear entry we wish to improve the transfer of genetic material into the cell. An important aspect is that the functional entities should also have tissue-targeting properties in vivo. Examples of functional entities investigated to date are the Simian virus 40 nuclear localisation signal to improve nuclear uptake and different carbohydrate ligands in order to achieve receptor specific uptake. The delivery system is also endowed with regulatory capability, since the release of functional entities can be controlled. The aim is to create a safe, pharmaceutically defined and stable delivery system for nucleic acids with enhanced transfection properties that can be used in the clinic.

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Adding functional entities to plasmids

Cited by 23 publications

References 28 publications

Nanotechnology approaches for gene transfer

Nanotechnology approaches for gene transfer

Semisynthetic DNA-protein conjugates for fabrication of nucleic acid based nanostructures

Bioplex Technology: Novel Synthetic Gene Delivery Pharmaceutical Based on Peptides Anchored to Nucleic Acids

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