Evidence of DNA transfer across a model membrane by a neutral amphiphilic block copolymer

Huin, Cécile; Gall, Tony Le; Barteau, Benoit; Pitard, Bruno; Montier, Tristan; Lehn, Pierre; Cheradame, Hervé; Guégan, Philippe

doi:10.1002/jgm.1612

Cited by 13 publications

(16 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…BLM revealed that the active concentration of the copolymers was in the range of 10–100 µg mL −1 , lower than the one used for fluorescence experiments and in vivo assays. TBCPs destabilize the lipid membrane but the permeation mechanism is not well‐defined, as already mentioned for other amphiphilic copolymers 55,57,58. The Hill plot indicated that only one macromolecule can induce the pore formation, which is in line with their unimer phase at this concentration.…”

Section: Discussionmentioning

confidence: 76%

“…On the histogram profile, the population present at 0 pA corresponds to the lipid membrane (insulator). Then, a population of different events, at almost all the currents, was observed indicating that the structures of permeation are not well‐defined, as already mentioned by using amphiphilic copolymers in presence of lipid membrane 55,57,58…”

Section: Resultsmentioning

confidence: 90%

“…TBCPs alone were first studied with the diphytanoylphosphatidylcholine model membrane, a standard phospholipid found in the skeletal muscle membrane57 ( Figure 6 ). Auvray and co‐workers,55 reported that Lutrol forms nanopores in such membrane through a carpet mechanism, involving few PEO‐ b ‐PPO‐ b ‐PEO molecules.…”

Section: Resultsmentioning

confidence: 99%

“…Interactions of TBCPs with a lipid membrane model made of diphytanoylphosphatidylcholine (Avanti Polar Lipids, Inc.) were studied according to the “Black Lipid Membrane” (BLM) technique 57. The electrolyte used was a 1 m KCl (the measured intensity is related to the salt concentration, and this salt concentration is required to get enough information in the data analysis step), 5 m m HEPES, buffer pH 7.4.…”

Section: Methodsmentioning

confidence: 99%

“…Sahay et al ascertained that the internalization pathway of Pluronic P85 in mammalian cells happens through endocytosis: Unimers are internalized through caveolae‐mediated endocytosis, while micelles (and their payload) are internalized through clathrin‐mediated endocytosis 53. Another assumption to explain the transfection efficiency is based on the ability of amphiphilic copolymers to span membrane lipid bilayers and to form transient pores 54–62…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Temperature‐Sensitive Amphiphilic Non‐Ionic Triblock Copolymers for Enhanced In Vivo Skeletal Muscle Transfection

Rasolonjatovo

Illy

Bennevault

et al. 2020

Macromolecular Bioscience

Self Cite

View full text Add to dashboard Cite

It is reported that low concentration of amphiphilic triblock copolymers of pMeOx‐b‐pTHF‐b‐pMeOx structure (TBCPs) improves gene expression in skeletal muscle upon intramuscular co‐injection with plasmid DNA. Physicochemical studies carried out to understand the involved mechanism show that a phase transition of TBCPs under their unimer state is induced when the temperature is elevated from 25 to 37 °C, the body temperature. Several lines of evidences suggest that TBCP insertion in a lipid bilayer causes enough lipid bilayer destabilization and even pore formation, a phenomenon heightened during the phase transition of TBCPs. Interestingly, this property allows DNA translocation across the lipid bilayer model. Overall, the results indicate that TBCPs exhibiting a phase transition at the body temperature is promising to favor in vivo pDNA translocation in skeletal muscle cells for gene therapy applications.

show abstract

Section: Discussionmentioning

confidence: 76%

Section: Resultsmentioning

confidence: 90%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Temperature‐Sensitive Amphiphilic Non‐Ionic Triblock Copolymers for Enhanced In Vivo Skeletal Muscle Transfection

Rasolonjatovo

Illy

Bennevault

et al. 2020

Macromolecular Bioscience

Self Cite

View full text Add to dashboard Cite

show abstract

Gene transfer to skeletal muscle using hydrodynamic limb vein injection: current applications, hurdles and possible optimizations

Guen

Gall

Midoux

et al. 2020

The Journal of Gene Medicine

Self Cite

View full text Add to dashboard Cite

Hydrodynamic limb vein injection is an in vivo locoregional gene delivery method. It consists of administrating a large volume of solution containing nucleic acid constructs in a limb with both blood inflow and outflow temporarily blocked using a tourniquet. The fast, high pressure delivery allows the musculature of the whole limb to be reached. The skeletal muscle is a tissue of choice for a variety of gene transfer applications, including gene therapy for Duchenne muscular dystrophy or other myopathies, as well as for the production of antibodies or other proteins with broad therapeutic effects. Hydrodynamic limb vein delivery has been evaluated with success in a large range of animal models. It has also proven to be safe and welltolerated in muscular dystrophy patients, thus supporting its translation to the clinic.However, some possible limitations may occur at different steps of the delivery process. Here, we have highlighted the interests, bottlenecks and potential improvements that could further optimize non-viral gene transfer following hydrodynamic limb vein injection. K E Y W O R D Sgene transfer, hydrodynamic delivery, locoregional, non-viral gene delivery, optimizations, skeletal muscle

show abstract

Neutral Block Copolymer Assisted Gene Delivery using Hydrodynamic Limb Vein Injection

Guen,

Delecourt,

Gall

et al. 2024

Macromolecular Bioscience

View full text Add to dashboard Cite

Three different amphiphilic block copolymer families were synthesized to investigate new opportunities to enhance gene delivery via Hydrodynamic Limb Vein (HLV) injections. First a polyoxazoline‐based family containing mostly one poly(2‐methyl‐2‐oxazoline) (PMeOx) block and a second block POx with an ethyl (EtOx), isopropyl (iPrOx) or phenyl substituent (PhOx) has been synthesized. Then an ABC poly(2‐ethyl‐2‐oxazoline)‐b‐poly(2‐n‐propyl‐2‐oxazoline)‐b‐poly(2‐methyl‐2‐oxazoline) triblock copolymer was synthesized, with a thermosensitive middle block. Finally, polyglycidol‐b‐polybutylenoxide‐b‐polyglycidol copolymers with various molar masses and amphiphilic balance were produced. The simple architecture of neutral amphiphilic triblock copolymer is not sufficient to obtain enhanced in vivo gene transfection. Double or triple amphiphilic neutral block copolymers are improving the in vivo transfection performances through HLV administration as far as a block having an LCST is incorporated in the vector. The molar mass of the copolymer does not seem to affect the vector performances in a significant manner.This article is protected by copyright. All rights reserved

show abstract

Evidence of DNA transfer across a model membrane by a neutral amphiphilic block copolymer

Abstract: These results strongly suggest that gene transfection by neutral block copolymers may involve the formation of cellular pores; in addition, they also highlight that in vivo gene transfection requires the use of adequately soluble block copolymers.

Cited by 13 publications

References 33 publications

Temperature‐Sensitive Amphiphilic Non‐Ionic Triblock Copolymers for Enhanced In Vivo Skeletal Muscle Transfection

Temperature‐Sensitive Amphiphilic Non‐Ionic Triblock Copolymers for Enhanced In Vivo Skeletal Muscle Transfection

Gene transfer to skeletal muscle using hydrodynamic limb vein injection: current applications, hurdles and possible optimizations

Neutral Block Copolymer Assisted Gene Delivery using Hydrodynamic Limb Vein Injection

Contact Info

Product

Resources

About