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Delivery of short i...
Delivery of short interfering RNA using endosomolytic cell-penetrating peptides
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- Lundberg, Pontus (författare)
- Stockholms universitet,Institutionen för neurokemi
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- EL Andaloussi, Samir (författare)
- Stockholms universitet,Institutionen för neurokemi
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- Sütlü, Tolga (författare)
- Stockholms universitet,Institutionen för neurokemi
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- Johansson, Henrik (författare)
- Stockholms universitet,Institutionen för neurokemi
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- Langel, Ülo (författare)
- Stockholms universitet,Institutionen för neurokemi
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(creator_code:org_t)
- 2007-04-26
- 2007
- Engelska.
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Ingår i: The FASEB Journal. - : Wiley. - 0892-6638 .- 1530-6860. ; 21:11, s. 2664-2671
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Cell-penetrating peptides (CPPs) are peptides able to promote uptake of various cargos, including proteins and plasmids. Advances in recent years imply the uptake to be endocytic, where the current hurdle for efficient intracellular delivery is material being retained in the endosomes. In this study we wanted to compare the ability of various established CPPs to deliver siRNA and induce gene silencing of luciferase, with a novel designed penetratin analog having endosomolytic properties, using a noncovalent strategy. In principal, the penetratin analog EB1 will, upon protonation in the early-late endosomes, be able to form an amphipathic alpha helix resulting in permeabilization of the endosomal membrane. We demonstrate that even though all CPPs evaluated in this study can form complexes with siRNA, there is not a direct relationship between the complex formation ability and delivery efficacy. More important, although all CPPs significantly promote siRNA uptake, in some cases no gene silencing effect can be observed unless endosomal escape is induced. We find the designed endosomolytic peptide EB1 to be far more effective both in forming complexes and transporting biologically active siRNA than its parent peptide penetratin. We believe that developing CPPs with increased endosomolytical properties is a necessary step toward achieving biological effects at low concentrations for future in vivo applications.—Lundberg, P., El-Andaloussi, S., Sütlü, T., Johansson, H., Langel, Ü. Delivery of short interfering RNA using endosomolytic cell-penetrating peptides.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
- NATURVETENSKAP -- Kemi (hsv//swe)
- NATURAL SCIENCES -- Chemical Sciences (hsv//eng)
Nyckelord
- CPP
- gene silencing
- siRNA
- oligonucleotides
- RNA interference
- Neurochemistry
- Neurokemi
- Chemistry
- Kemi
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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