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Differences in DNA ...
Differences in DNA Condensation and Release by Lysine and Arginine Homopeptides Govern Their DNA Delivery Efficiencies
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Mann, Anita (author)
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Thakur, Garima (author)
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Shukla, Vasundhara (author)
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Singh, Anand Kamal (author)
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Khanduri, Richa (author)
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Naik, Rangeetha (author)
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- Jiang, Yang (author)
- Stockholms universitet,Institutionen för neurokemi
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Kalra, Namita (author)
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Dwarakanath, B. S. (author)
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- Langel, Ulo (author)
- Stockholms universitet,Institutionen för neurokemi
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Ganguli, Munia (author)
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(creator_code:org_t)
- 2011-08-05
- 2011
- English.
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In: Molecular Pharmaceutics. - : American Chemical Society (ACS). - 1543-8384 .- 1543-8392. ; 8:5, s. 1729-1741
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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- Designing of nanocarriers that can efficiently deliver therapeutic DNA payload and allow its smooth intracellular release for transgene expression is still a major constraint. The optimization of DNA nanocarriers requires thorough understanding of the chemical and structural characteristics of the vector-nucleic acid complexes and its correlation with the cellular entry, intracellular state and transfection efficiency. L-Lysine and L-arginine based cationic peptides alone or in conjugation with other vectors are known to be putative DNA delivery agents. Here we have used L-lysine and L-arginine homopeptides of three different lengths and probed their DNA condensation and release properties by using a multitude of biophysical techniques including fluorescence spectroscopy, gel electrophoresis and atomic force microscopy. Our results clearly showed that although both lysine and arginine based homopeptides condense DNA via electrostatic interactions, they follow different pattern of DNA condensation and release in vitro. While lysine homopeptides condense DNA to form both monomolecular and multimolecular complexes and show differential release of DNA in vitro depending on the peptide length, arginine homopeptides predominantly form multimolecular complexes and show complete DNA release for all peptide lengths. The cellular uptake of the complexes and their intracellular state (as observed through flow cytometry and fluorescence microscopy) seem to be controlled by the peptide chemistry. The difference in the transfection efficiency of lysine and arginine homopeptides has been rationalized in light of these observations.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
- NATURVETENSKAP -- Kemi (hsv//swe)
- NATURAL SCIENCES -- Chemical Sciences (hsv//eng)
Keyword
- nonviral gene delivery
- cationic peptides
- DNA condensation
- atomic force microscopy
- condensation-release balance
- structure-activity correlation
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Mann, Anita
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Thakur, Garima
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Shukla, Vasundha ...
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Singh, Anand Kam ...
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Khanduri, Richa
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Naik, Rangeetha
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show more...
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Jiang, Yang
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Kalra, Namita
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Dwarakanath, B. ...
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Langel, Ulo
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Ganguli, Munia
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Pharmaceutical S ...
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Chemical Science ...
- Articles in the publication
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Molecular Pharma ...
- By the university
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Stockholm University