+ Resolve Article
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter

+ Translate
+ Subscribe to Site Feed
GeoScience Most Shared ContentMost Shared Content

Polyplexes traffic through caveolae to the Golgi and endoplasmic reticulum en route to the nucleus

, : Polyplexes traffic through caveolae to the Golgi and endoplasmic reticulum en route to the nucleus. Molecular Pharmaceutics 9(5): 1280-1290

The cellular machinery involved in the internalization of nonviral gene carriers and their subsequent trafficking to the nucleus directly impacts their therapeutic efficiency. Hence, identifying key endocytic pathways and organelles that contribute to the successful transfer of polyplexes to the nucleus generates new opportunities for improving carrier design. Previously, we showed that histone H3 tail peptides encoding a sequence known to participate in chromatin activation exhibit synergistic gene delivery activity with poly(ethylenimine) (PEI). Polyplexes containing H3 and PEI exhibited a reduced dependence on endocytic pathways that trafficked to lysosomes, and had enhanced sensitivity to an inhibitor associated with retrograde trafficking through the Golgi apparatus. Thus, we sought to determine whether caveolar uptake and transport through the Golgi and/or endoplasmic reticulum (ER) preceded nuclear delivery. By the use of a panel of chemical endocytic inhibitors, we determined that H3 polyplexes utilized caveolar pathways to a greater degree than PEI polyplexes. Caveolae-mediated endocytosis was found to be a productive route for gene expression by the H3/PEI-pDNA polyplexes, consistent with previous studies of polymer-mediated gene delivery. Additionally, the polyplexes substantially colocalized within the ER after only 5 min of incubation, and utilized retrograde Golgi-to-ER pathways at levels similar to pathogens known to traffic by these routes during infection. The results of this study have expanded our understanding of how caveolar polyplexes are trafficked to cell nuclei, and provide new evidence for the role of Golgi-ER pathways in transfection. These findings suggest new design criteria and opportunities to stragetically target nonviral gene delivery vehicles.


PMID: 22420286

DOI: 10.1021/mp200583d

Other references

Lehtinen Pentti V., 1992: Earth and concrete engineering. Special Paper - Geological Survey of Finland 15: 141-145

Wéber, Ió.; Veress, Gábor.; Szucs, Péter.; Antal, Mós.; Birinyi, Aás., 2007: Neurotransmitter systems of commissural interneurons in the lumbar spinal cord of neonatal rats. The circuits that generate rhythmic locomotor activities are located in the ventromedial area of the lumbar spinal cord and comprise commissural interneurons necessary for left-right alternation during walking movements. In this study we injected...

Talha, M.; Abo Gabal, E.;, E.M.; E.G.any, M.B.A., 1993: Use of non-steady state equation to predict hydraulic head in soils provided with tile drainage. Egyptian Journal of Soil Science 33(3): 257-266

Davies, J.N.; Owen, O., 1951: Soil sterilization. I. Ammonia and nitrate production in some glasshouse soils following steam sterilization. Ammonia production and subsequent nitrate formation were studied in several types of glasshouse soils after partial sterilization by steam. Where the soil was steamed in situ and left undisturbed ammonia production was stimulated and continued for...

Morris, H.A.L.; Neff, E.; Latimer, G.B., 1967: The occurrence of crystalline lactose in skim milk powder from a commercial factory. In the past it has been accepted that lactose occurs in milk powder as an amorphous glass. However, numerous observations were recently made of the occurrence of crystalline lactose in skim milk powders from one factory. This is attributed to lact...

Hertel, I.V.; Shchatsinin, I.; Laarmann, T.; Zhavoronkov, N.; Ritze, H-H.; Schulz, C.P., 2009: Fragmentation and ionization dynamics of C60 in elliptically polarized femtosecond laser fields. Ionization and fragmentation of C60 fullerenes is studied in elliptically polarized, intense fs laser fields at 797 nm [I=(0.5-4.3)x10;{14} W cm;{-2}] and contrasted with Xe+, utilizing time-of-flight mass spectrometry. Very pronounced changes of...

Gailly P., 1990: The effect of brevin on unloaded shortening of isolated smooth muscle cells. Archives Internationales de Physiologie et de Biochimie 98(1): P22

Baxendale W., 1971: Studies of 3 avian pox viruses and the development of an improved fowl pox vaccine. Veterinary Record 88(1): 5-10

Timothy A.Dickinson, 1998: Taxonomy of agamic complexes in plants A role for metapopulation thinking. The argument is made that species should be comparable with respect to the numbers of genotypes they include, regardless of whether their reproduction is exclusively sexual or not. Specifically, this means recognizing species at a level comparable...

Zhavoronkova, OD., 1978: On the vertical distribution of Bosmina longispina and B. coregoni.. Biologiya Vnutrennikh Vod Informatsionnyi Byulleten': 52-55 No. 38