Chondroitin sulfate increases cell transfection efficiency by DNA-PEI complexes

Bulanenkova S.S.; Snezhkov E.V.; Potapov V.K.; Akopov S.B.; Sverdlov E.D.

doi:https://doi.org/10.17116/molgen201937041178

Bulanenkova S.S.

Shemyakin—Ovchinnikov Institute of Bioorganic Chemistry RAS, Moscow, Russia, 117997

Snezhkov E.V.

Shemyakin—Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow, Russia, 117997

Potapov V.K.

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, Mikluho-Maklaya 16/10, Moscow 117997, Russia

Akopov S.B.

Shemyakin—Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow, Russia, 117997

Sverdlov E.D.

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, Mikluho-Maklaya 16/10, Moscow 117997, Russia;
Institute of Molecular Genetics RAS, Kurchatov sq. 2, Moscow 123182, Russia

Chondroitin sulfate increases cell transfection efficiency by DNA-PEI complexes

Authors:

Bulanenkova S.S., Snezhkov E.V., Potapov V.K., Akopov S.B., Sverdlov E.D.

More about the authors

Journal: Molecular Genetics, Microbiology and Virology. 2019;37(4): 178‑185

DOI: 10.17116/molgen201937041178

Read: 1869 times

Download PDF (RU)

Contact the author

Table of contents

To cite this article:

Bulanenkova SS, Snezhkov EV, Potapov VK, Akopov SB, Bulanenkova SS, Sverdlov ED. Chondroitin sulfate increases cell transfection efficiency by DNA-PEI complexes. Molecular Genetics, Microbiology and Virology. 2019;37(4):178‑185. (In Russ.)
https://doi.org/10.17116/molgen201937041178

Подписка 2026 Молекулярная генетика, микробиология и вирусология (Molecular Genetics, Microbiology and Virology)

Использование инфографики авторами научных работ

Close metadata

Recommended articles:

DNA base editors are a promising tool to gene therapy of human viral infections. Molecular Genetics, Microbiology and Virology. 2025;(3):4-8

Comparison of media components and reagents in cultivation and genetic editing of human cells A549. Molecular Genetics, Microbiology and Virology. 2025;(4-2):135-142

Comparative evaluation of oral chondroprotectors effectiveness in patients with low back pain. S.S. Korsakov Journal of Neurology and Psychiatry. 2025;(7):98-103

Influence of limb revascularization and therapeutic angiogenesis on concentration of angiogenic factors. Russian Journal of Cardiology and Cardiovascular Surgery. 2025;(5):539-546

First experience of the application of beremagene geperpavec genetically engineered drug for treatment of congenital dystrophic epidermolysis bullosa in the Russian Federation. Russian Journal of Clinical Dermatology and Venereology. 2025;(6):822-827

Ways to optimize the management of lower back pain patients at the outpatient stage. S.S. Korsakov Journal of Neurology and Psychiatry. 2025;(12):148-153

Abstract:

Introduction. One of the most popular non-viral delivery systems for the gene therapy constructs are the DNA complexes with polyethylenimine (PEI)-based carriers. A number of disadvantages associated with the lack of targeted delivery and increased cytotoxicity are overcome by the addition of auxiliary molecules to the complexes. An example is the chondroitin sulfate (hereinafter CS). The purpose of this work was to assess the effect of CS on the transfection properties of the DNA-PEI complexes under different conditions of their preparation and transfection protocols. Methods. All complexes were prepared in solutions with high and low ionic strength. Transfection of C26 cells was performed according to two protocols differing in the presence of serum in the medium. The portion of transfected cells, transgene expression level and cell viability were the main parameters of assessing the transfection efficiency. Results. In the binary DNA-PEI complexes prepared in different salt conditions, using different transfection protocols, the difference in the portion of transfected cells reached 10 times. Addition of the CS improved this transfection efficiency indicator up to 6.5 times, while the maximum difference in this indicator for the corresponding ternary complexes was reduced to 2.5 times. Changes in the proportion of CS in the composition of the complexes had little effect on their transfection properties. In the case of the complexes prepared in high ionic strength solutions, the order of CS addition was also important. The best results of transfection efficiency were achieved with ternary complexes prepared in low ionic strength solutions, using a serum-free protocol, while these indicators were comparable with the data for Lipofectamine 2000. Conclusion. The addition of chondroitin sulfate improves the transfection properties of DNA-PEI complexes and makes them less dependent on the methods of preparation and transfection.

Keywords:

polyethyleneimine

chondroitin sulfate

transfection

serum

ionic strength of solution

gene therapy

polyplex

carrier

Authors:

Bulanenkova S.S.

Shemyakin—Ovchinnikov Institute of Bioorganic Chemistry RAS, Moscow, Russia, 117997

Snezhkov E.V.

Shemyakin—Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow, Russia, 117997

Potapov V.K.

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, Mikluho-Maklaya 16/10, Moscow 117997, Russia

Akopov S.B.

Shemyakin—Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow, Russia, 117997

Sverdlov E.D.

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, Mikluho-Maklaya 16/10, Moscow 117997, Russia;
Institute of Molecular Genetics RAS, Kurchatov sq. 2, Moscow 123182, Russia

Close metadata

References:

Asad AS, Ayala MAM, Gottardo MF, Zuccato C, Javier A, Candia N, et al. Viral gene therapy for breast cancer: progress and challenges. Expert Opin Biol Ther. 2017;17(8):945-959. https://doi.org/10.1080/14712598.2017.1338684
Samal SK, Dash M, Vlierberghe S Van, Kaplan DL, Chiellini E, Blitterswijk C Van, et al. Cationic polymers and their therapeutic potential. Chem Soc Rev. 2012;41(21):7147-7194. https://doi.org/10.1039/c2cs35094g
Boussif O, Lezoualc’h F, Zanta M, Mergny M, Schermant D, Demeneixt B, et al. A versatile vector for gene and oligonucleotide transfer into cells in culture and in vivo: Polyethylenimine. Proc Natl Acad Sci USA. 1995;92(16): 7297-7301. https://doi.org/10.1073/pnas.92.16.7297
Kircheis R, Wightman L, Wagner E. Design and gene delivery activity of modified polyethylenimines. Adv Drug Deliv Rev. 2001;53(3):341-358. https://doi.org/10.1016/S0169-409X(01)00202-2
Hall A, Lächelt U, Bartek J, Wagner E, Moghimi SM. Polyplex Evolution : Understanding Biology, Optimizing Performance. Mol Ther. 2017;25(7): 1-15. https://doi.org/10.1016/j.ymthe.2017.01.024
Ruponen M, Ylä-Herttuala S, Urtti A. Interactions of polymeric and liposomal gene delivery systems with extracellular glycosaminoglycans: Physicochemical and transfection studies. Biochim Biophys Acta — Biomembr. 1999;1415(2):331-341. https://doi.org/10.1016/S0005-2736(98)00199-0
Plank C, Mechtler K, Szoka FJ, Wagner E. Activation of the complement system by synthetic DNA complexes: a potential barrier for intravenous gene delivery. Hum Gene Ther. 1996;7(12):1437-1446. https://doi.org/10.1089/hum.1996.7.12-1437
Coll J, Chollet P, Brambilla E, Desplanques D, Behr J, Favrot M. In vivo Delivery to Tumors of DNA Complexed with Linear Polyethylenimine. Hum Gene Ther. 1999;10(10):1659-1666. https://doi.org/10.1089/10430349950017662
Ogris M, Brunner S, Schu S, Kircheis R, Wagner E. PEGylated DNA/transferrin — PEI complexes : reduced interaction with blood components, extended circulation in blood and potential for systemic gene delivery. Gene Ther. 1999;6(4):595-605. https://doi.org/10.1038/sj.gt.3300900
Ulasov AV, Khramtsov YV, Trusov GA, Rosenkranz AA, Sverdlov ED, Sobolev AS. Properties of PEI-based polyplex nanoparticles that correlate with their transfection efficacy. Mol Ther. 2011;19(1):103-112. https://doi.org/10.1038/mt.2010.233
Alekseenko IV, Snezhkov EV, Chernov IP, Pleshkan VV, Potapov VK, Sass AV, et al. Therapeutic properties of a vector carrying the HSV thymidine kinase and GM-CSF genes and delivered as a complex with a cationic copolymer. J Transl Med. 2015;13(1):1-16. https://doi.org/10.1186/s12967-015-0433-0
Pathak A, Kumar P, Chuttani K, Jain S, Mishra AK, Vyas SP, et al. Gene expression, biodistribution, and pharmacoscintigraphic evaluation of chondroitin sulfate-PEI nanoconstructs mediated tumor gene therapy. ACS Nano. 2009;3(6):1493-1505. https://doi.org/10.1021/nn900044f
Kurosaki T, Kitahara T, Kawakami S, Nishida K, Nakamura J, Teshima M, et al. The development of a gene vector electrostatically assembled with a polysaccharide capsule. Biomaterials. 2009;30(26):4427-4434. https://doi.org/10.1016/j.biomaterials.2009.04.041
Ito T, Iida-Tanaka N, Koyama Y. Efficient in vivo gene transfection by stable DNA/PEI complexes coated by hyaluronic acid. J Drug Target. 2008;16(4):276-281. https://doi.org/10.1080/10611860801900728
Underhill C. CD44 : The hyaluronan receptor. J Cell Sci. 1992;103:293-238.
Chen C, Zhao S, Karnad A, Freeman JW. The biology and role of CD44 in cancer progression : therapeutic implications. J Hematol Oncol. 2018;11(1):1-23. https://doi.org/10.1186/s13045-018-0605-5
Kinugasa Y, Matsui T, Takakura N. CD44 expressed on cancer-associated fibroblasts is a functional molecule supporting the stemness and drug resistance of malignant cancer cells in the tumor microenvironment. Stem Cells. 2014;32(1):145-156. https://doi.org/10.1002/stem.1556
Lo YL, Sung KH, Chiu CC, Wang LF. Chemically conjugating polyethylenimine with chondroitin sulfate to promote CD44-mediated endocytosis for gene delivery. Mol Pharm. 2013;10(2):664-676. https://doi.org/10.1021/mp300432s
Dubey RD, Klippstein R, Wang JT-W, Hodgins N, Mei K-C, Sosabowski J, et al. Novel Hyaluronic Acid Conjugates for Dual Nuclear Imaging and Therapy in CD44-Expressing Tumors in Mice In vivo. Nanotheranostics. 2017;1(1):59-79. https://doi.org/10.7150/ntno.17896
Guillem VM, Aliño SF. Transfection pathways of nonspecific and targeted PEI-polyplexes. Gene Ther Mol Biol. 2004;8:369-384.
Ogris M, Steinlein P, Kursa M, Mechtler K, Kircheis R, Wagner E. The size of DNA/transferrin-PEI complexes is an important factor for gene expression in cultured cells. Gene Ther. 1998;5(10):1425-1433. https://doi.org/10.1038/sj.gt.3300745
Wightman L, Kircheis R, Carotta S, Ruzicka R, Kursa M, Wagner E. Different behavior of branched and linear polyethylenimine for gene delivery in vitro and in vivo. J Gene Med. 2001;3(4):362-372. https://doi.org/10.1002/jgm.187
Song H, Wang G, He B, Li L, Li C, Lai Y, et al. Cationic lipid-coated PEI/DNA polyplexes with improved efficiency and reduced cytotoxicity for gene delivery into mesenchymal stem cells. Int J Nanomedicine. 2012;7:4637-4648. https://doi.org/10.2147/IJN.S33923
Guo W, Lee RJ. Efficient gene delivery via non-covalent complexes of folic acid and polyethylenimine. J Control Release. 2001;77:131-138. https://doi.org/10.1016/S0168-3659(01)00456-4
Cheraghi R, Alipour M, Nazari M, Hosseinkhani S. Optimization of conditions for gene delivery system based on PEI. Nanomedicine J. 2017;4(1):8-16. https://doi.org/10.22038/nmj.2017.8047
Koyama Y, Sugiura K, Yoshihara C, Inaba T, Ito T. Highly effective non-viral antitumor gene therapy system comprised of biocompatible small plasmid complex particles consisting of pDNA, anionic polysaccharide, and fully deprotected linear polyethylenimine. Pharmaceutics. 2015;7(3):152-164. https://doi.org/10.3390/pharmaceutics7030152
Breunig M, Lungwitz U, Liebl R, Goepferich A. Breaking up the correlation between efficacy and toxicity for nonviral gene delivery. Proc Natl Acad Sci USA. 2007;104(36):14454-14459. https://doi.org/10.1073/pnas.0703882104