Abstract
In order to correct the genetic defects that are fundamental reasons for many pathologies, gene therapy uses exogenous nucleic acids for intentional modulation of gene expression in specific cells. Due to the large size and the negative charge of exogenous nucleic acids, the delivery of these macromolecules is typically mediated by carriers or vectors. Viral carriers are known to be very efficient however, they have a severe drawbacks such as toxicity and immunogenicity. In this regard, gene-based therapy using non-viral approaches has drawn increasing attention, and has become an important field of research. The diversity of materials used as of non-viral vectors known today highlights the recent progress of gene-based therapy using non-viral approaches. Herein, we describe the progress made by our group in the development of hybrid vectors that combine key features of classical carriers design rationally or formed by combinatorial approach using dynamic chemistry which are remarkable strategies to address the current challenges in gene delivery.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Abbreviations
- pDNA:
-
Plasmid DNA
- siRNA:
-
Small interfering RNA
- β-CD:
-
β-Cyclodextrin
- bPEI:
-
Branched poly(ethyleneimine)
- PEG:
-
Poly(ethylene glycol)
- pLuc:
-
Luciferase plasmid
- pGFP:
-
Green fluorescent protein plasmid
- CDC:
-
Constitutional dynamic chemistry
- DCF:
-
Dynamical constitutional frameworks
- dsDN:
-
Duble stranded DNA
- TE:
-
Transfection efficiency
- Girard’s reagent T:
-
(Carboxymethyl)trimethylammonium chloride hydrazide
- HeLa:
-
Human cervix adenocarcinoma
- DF:
-
Dynameric frameworks
- HEK 293T:
-
Human embryonic kidney 293T cells
- pEGFP:
-
Enhanced green fluorescent protein plasmid
- N/P:
-
Nitrogen/phosphorus
- AFM:
-
Atomic force microscopy
References
Ailincai D, Marin L, Morariu S et al (2016) Dual crosslinked iminoboronate-chitosan hydrogels with strong antifungal activity against Candida planktonic yeasts and biofilms Carbohyd Polym 152:306–316
Ailincai D, Tartau Mititelu L, Marin L (2018) Drug delivery systems based on biocompatible imino-chitosan hydrogels for local anticancer therapy. Drug Deliv. 25(1):1080–1090
Ailincai D, Peptanariu D, Pinteala M et al (2019) Dynamic constitutional chemistry towards efficient nonviral vectors Mater Sci Eng C 94:635–646
Ardeleanu R, Dascalu AI, Neamtu A et al (2018) Multivalent polyrotaxane vectors as adaptive cargo complexes for gene therapy. Polym Chem 9(7):845–859
Bainbridge JWB, Tan MH, Ali RR (2006) Gene therapy progress and prospects: the eye. Gene Ther 13(16):1191–1197
Banks WA (2009) Characteristics of compounds that cross the blood-brain barrier. BMC Neurol 9(1):S3
Cam C, Segura T (2013) Matrix-based gene delivery for tissue repair. Curr Opin Biotech 24(5):855–863
Catana R, Barboiu M, Moleavin I et al (2015) Dynamic constitutional frameworks for DNA biomimetic recognition. Chem Commun 51(11):2021–2024
Clima L, Peptanariu D, Pinteala M et al (2015) DyNAvectors: dynamic constitutional vectors for adaptive DNA transfection. Chem Commun 51(99):17529–17531
Clima L, Craciun BF, Gavril G et al (2019) Tunable composition of dynamic non-viral vectors over the DNA polyplex formation and nucleic acid transfection. Polymers 11(8):1313
Couvreur P (2009) “Squalenoylation”: a new approach to the design of anticancer and antiviral nanomedicines. B Acad Nat Med Paris 193(3):663–673
Craciun BF, Vasiliu T, Marangoci N et al (2018) Pegylated squalene: a biocomptible polymer as precursor for drug delivery. Rev Roum Chim 63(7–8):621–628
Craciun FB, Gavril G, Peptanariu D et al (2019) synergistic effect of low molecular weight polyethylenimine and polyethylene glycol components in dynamic nonviral vector structure, toxicity, and transfection efficiency. Molecules 24(8)
Dascalu AI, Ardeleanu R, Neamtu A et al (2017) Transfection-capable polycationic nanovectors which include PEGylated-cyclodextrin structural units: a new synthesis pathway. J Mater Chem B 5(34):7164–7174
Desmaele D, Gref R, Couvreur P (2012) Squalenoylation: a generic platform for nanoparticular drug delivery. J Control Release 161(2):609–618
Dunbar CE, High KA, Joung JK et al (2018) Gene therapy comes of age. Science 359(6372):eaan4672
Egger G, Liang G, Aparicio A et al (2004) Epigenetics in human disease and prospects for epigenetic therapy. Nature 429(6990):457–463
Elouahabi A, Ruysschaert J-M (2005) Formation and intracellular trafficking of lipoplexes and polyplexes. Mol Ther 11(3):336–347
Finbloom JA, Sousa F, Stevens MM et al (2020) Engineering the drug carrier biointerface to overcome biological barriers to drug delivery. Adv Drug Deliv Rev 167:89–108
Funhoff AM, van Nostrum CF, Koning GA et al (2004) Endosomal escape of polymeric gene delivery complexes is not always enhanced by polymers buffering at low pH. Biomacromol 5(1):32–39
Ginn SL, Amaya AK, Alexander IE et al (2018) Gene therapy clinical trials worldwide to 2017: an update. J Gene Med 20(5):e3015
Godbey WT, Barry MA, Saggau P et al (2000) Poly(ethylenimine)-mediated transfection: a new paradigm for gene delivery Journal of Biomedical Materials Research 51(3):321–328
Gordon R, Ranjith R, Leighann S et al (2012) Fungal Biofilm resistance. Int J Microbiol 2012
Hanna E, Rémuzat C, Auquier P et al (2017) Gene therapies development: slow progress and promising prospect. J Mark Access Health Policy 5(1):1265293
Harada A, Okada M, Kawaguchi Y et al (1999) Macromolecular recognition: new cyclodextrin polyrotaxanes and molecular tubes. Polym Adv Technol 10(1–2):3–12
Hedman M, Hartikainen J, Ylä-Herttuala S (2011) Progress and prospects: hurdles to cardiovascular gene therapy clinical trials. Gene Ther 18(8):743–749
Jiří V, Edward SW, Andrey Y et al (2012) Terminology and nomenclature for macromolecular rotaxanes and pseudorotaxanes (IUPAC Recommendations 2012). Pure Appl Chem 84(10):2135–2165
Kumar V, Qin J, Jiang Y et al (2014) Shielding of lipid nanoparticles for sirna delivery: impact on physicochemical properties, cytokine induction, and efficacy. Mol Ther Nucleic Acids 3(11):e210-e
Kursa M, Walker GF, Roessler V et al (2003) Novel shielded transferrin−polyethylene glycol−polyethylenimine/DNA complexes for systemic tumor-targeted gene transfer. Bioconjug Chem 14(1):222–231
Lehn J-M (2012) Constitutional dynamic chemistry. Barboiu M (ed.) Springer, Heidelberg, p 1–32
Lepeltier E, Bourgaux C, Rosilio V et al (2013) Self-assembly of squalene-based nucleolipids: relating the chemical structure of the bioconjugates to the architecture of the nanoparticles. Langmuir 29(48):14795–14803
Marin L, Ailincai D, Cahn M et al (2016) Dynameric frameworks for DNA transfection. ACS Biomater Sci Eng 2(1):104–111
Müller MM, Muir TW (2015) Histones: at the crossroads of peptide and protein chemistry. Chem Rev 115(6):2296–2349
Muramatsu S (2018) Gene therapy using adeno-associated virus vectors Cancer Sci 109(1200-.
Neu M, Fischer D, Kissel T (2005) Recent advances in rational gene transfer vector design based on poly(ethylene imine) and its derivatives. J Gene Med 7(8):992–1009
Neuberg P, Kichler A (2014) Advances in genetics. Huang L et al (eds) Academic Press, vol 88, pp 263–288
Olanow CW (2014) Gene therapy for Parkinson disease—a hope, or a dream? Nat Rev Neurol 10(4):186–187
Olden BR, Cheng YL, Yu JL et al (2018) Cationic polymers for non-viral gene delivery to human T cells. J Control Release 282:140–147
Papadopoulos KI, Wattanaarsakit P, Prasongchean W et al (2016) Polymers and nanomaterials for gene therapy. Narain R (ed) Woodhead Publishing, p 231–56
Paul A, Eun CJ, Song JM (2014) Cytotoxicity mechanism of non-viral carriers polyethylenimine and poly-L-lysine using real time high-content cellular assay. Polymer 55(20):5178–5188
Pricope G, Pinteala M, Clima L (2018) Dynamic self-organazing systems for DNA delivery. Rev Roum Chim 63(7–8):613–619
Semenza GL (2003) Targeting HIF-1 for cancer therapy. Nat Rev Cancer 3(10):721–732
Simionescu BC, Drobota M, Timpu D et al (2017) Biopolymers/poly(epsilon-caprolactone)/polyethylenimine functionalized nano-hydroxyapatite hybrid cryogel: Synthesis, characterization and application in gene delivery. Mat Sci Eng C-Mater 81:167–176
Smith AJ, Bainbridge JWB, Ali RR (2012) Gene supplementation therapy for recessive forms of inherited retinal dystrophies. Gene Ther 19(2):154–161
Somia N, Verma IM (2000) Gene therapy: trials and tribulations. Nat Rev. Genet 1(2):91–99
Suk JS, Xu Q, Kim N et al. (2016) PEGylation as a strategy for improving nanoparticle-based drug and gene delivery Adv Drug Deliver Rev 99:28–51
Thapa B, Narain R (2016) Polymers and nanomaterials for gene therapy. Narain R (ed) Woodhead Publishing, p 1–27
Tierney EG, Duffy GP, Cryan SA et al (2013) Non-viral gene-activated matrices next generation constructs for bone repair. Organogenesis 9(1):22–28
Turin-Moleavin IA, Doroftei F, Coroaba A et al (2015) Dynamic constitutional frameworks (DCFs) as nanovectors for cellular delivery of DNA. Org Biomol Chem 13(34):9005–9011
Uritu CM, Varganici CD, Ursu L et al (2015) Hybrid fullerene conjugates as vectors for DNA cell-delivery. J Mater Chem B 3(12):2433–2446
Uritu CM, Calin M, Maier SS et al (2015) Flexible cyclic siloxane core enhances the transfection efficiency of polyethylenimine-based non-viral gene vectors. J Mater Chem B 3(42):8250–8267
Wang Y, Zheng M, Meng F et al (2011) Branched polyethylenimine derivatives with reductively cleavable periphery for safe and efficient in vitro gene transfer. Biomacromol 12(4):1032–1040
Wu P, Chen H, Jin R et al (2018) Non-viral gene delivery systems for tissue repair and regeneration. J Transl Med 16(1):29
Yang J, Liu H, Zhang X (2014) Design, preparation and application of nucleic acid delivery carriers. Biotechnol Adv 32(4):804–817
Yao WJ, Cheng X, Fu SX et al (2018) Low molecular weight polyethylenimine-grafted soybean protein gene carriers with low cytotoxicity and greatly improved transfection invitro. J Biomater Appl 32(7):957–966
Yin H, Kanasty RL, Eltoukhy AA et al (2014) Non-viral vectors for gene-based therapy. Nat Rev. Genet 15(8):541–555
Zakeri A, Kouhbanani MAJ, Beheshtkhoo N et al (2018) Polyethylenimine-based nanocarriers in co-delivery of drug and gene: a developing horizon. Nano Rev Exp 9(1):1488497
Zhang Y, Barboiu M (2016) Constitutional dynamic materials-toward natural selection of function. Chem Rev 116(3):809–834
Acknowledgements
This publication is part of a project that has received funding from the H2020 ERA Chairs Project no 667387: SupraChem Lab Laboratory of Supramolecular Chemistry for Adaptive Delivery Systems ERA Chair initiative.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Ethics declarations
The authors declare no conflict of interest.
Rights and permissions
Copyright information
© 2021 The Author(s), under exclusive license to Springer Nature Switzerland AG
About this chapter
Cite this chapter
Clima, L., Dascalu, A.I., Craciun, B.F., Pinteala, M. (2021). Polymeric Carriers for Transporting Nucleic Acids—Contributions to the Field. In: J.M. Abadie, M., Pinteala, M., Rotaru, A. (eds) New Trends in Macromolecular and Supramolecular Chemistry for Biological Applications. Springer, Cham. https://doi.org/10.1007/978-3-030-57456-7_7
Download citation
DOI: https://doi.org/10.1007/978-3-030-57456-7_7
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-030-57455-0
Online ISBN: 978-3-030-57456-7
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)