Abstract
The ultimate goal in siRNA formulation for regenerative application centers around a gradual and sustained local release of intact siRNA which is adapted to the physiological requirements of the specific tissue. Although various issues in optimizing the siRNA delivery systems in terms of safety and efficiency still need to be addressed, progress towards the potential translation of RNAi-based therapies to clinical use has been made. An increasing number of promising siRNA-based gene therapies is currently in, or advancing towards clinical trials. Looking back to a period of only 17 years since the discovery of RNAi (Fire A, Xu S, Montgomery MK, Kostas SA, Driver SE, Mello CC, Nature 391(6669):806–811. doi:10.1038/35888, 1998) and the introduction of siRNAs as the underlying principle of RNAi (Elbashir SM, Harborth J, Lendeckel W, Yalcin A, Weber K, Tuschl T, Nature 411(6836):494–498. doi:10.1038/35078107, 2001), it is likely that regenerative applications will be explored in clinical studies soon as well.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsAbbreviations
- ACI:
-
autologous chondrocyte implantation
- Ago:
-
argonaute protein
- BCL2:
-
B-cell lymphoma 2
- BMSCs:
-
bone marrow stromal cells
- cbfa1:
-
core binding factor alpha1
- CD:
-
cyclodextrin
- Chi:
-
chitosan
- Ckip-1:
-
casein kinase 2-interacting protein-1
- CPP:
-
cell penetrating peptide
- DOPE:
-
1,2-dioleoyl-glycero-3-phosphoethanolamine
- DOTAP:
-
1,2-dioleoyl-3-trimethylammonium-propane
- DOTMA:
-
1,2-di-O-octadecenyl-3-trimethylammonium propane
- ECs:
-
endothelial cells
- EEP:
-
ethyl ethylene phosphate
- EPR:
-
enhanced permeability and retention
- GNAS1:
-
guanine nucleotide-binding protein alpha-Stimulating activity polypeptide1
- HA:
-
hyaluronic acid
- hASCs:
-
human adipose stromal cells
- HIF-1:
-
hypoxia-inducible factor1
- HIV:
-
human immunodeficiency virus
- hMSCs:
-
human mesenchymal stem cells
- LbL:
-
layer by layer
- LSD1:
-
lysine (K)-specific demethylase 1A
- miRNA:
-
micro RNA
- NP:
-
nanoparticles
- PCL:
-
poly-ε-caprolactone
- PEC:
-
polyelectrolyte complex
- PEI:
-
polyethylenimine
- PEG:
-
polyethylene glycol
- PEMs:
-
polyelectrolyte multilayers
- PHD2:
-
prolyl hydroxylase domain protein 2
- PLGA:
-
poly(lactic-co-glycolic acid)
- PLA:
-
poly(L-lactic acid)
- PLK1:
-
tumor survival genes polo-like kinase 1
- PSMA:
-
progressive spinal muscular atrophy
- RANK:
-
receptor activator of NF-κB
- RNA:
-
ribonucleic acid
- RNAi:
-
RNA interference
- RSV:
-
respiratory syncytial virus
- sFIt-1:
-
soluble fms-like tyrosine kinase-1
- shRNA:
-
short hairpin RNA
- siRNA:
-
small interfering RNA
- TCP:
-
β-tricalcium phosphate
- TRIB2:
-
tribbles homolog 2
- VEGF:
-
Vascular Endothelial Growth Factor
References
Agrawal N, Dasaradhi PVN, Mohmmed A, Malhotra P, Bhatnagar RK, Mukherjee SK (2003) RNA interference: biology, mechanism, and applications. Microbiol Mol Biol Rev 67(4):657–685. doi:10.1128/MMBR.67.4.657-685.2003
Behr J-P (1997) The proton sponge: a trick to enter cells the viruses did not exploit. CHIMIA 51(3):34–36
Breunig M, Hozsa C, Lungwitz U, Watanabe K, Umeda I, Kato H, Goepferich A (2008) Mechanistic investigation of poly(ethylene imine)-based siRNA delivery: disulfide bonds boost intracellular release of the cargo. J Control Release 130(1):57–63. doi:10.1016/j.jconrel.2008.05.016
Burnett JC, Rossi JJ, Tiemann K (2011) Current progress of siRNA/shRNA therapeutics in clinical trials. Biotechnol J 6(9):1130–1146. doi:10.1002/biot.201100054
Buyens K, Smedt D, Stefaan C, Braeckmans K, Demeester J, Peeters L, van Grunsven LA et al (2012) Liposome based systems for systemic siRNA delivery: stability in blood sets the requirements for optimal carrier design. J Control Release 158(3):362–370. doi:10.1016/j.jconrel.2011.10.009
Cao H, Jiang X, Chai C, Chew SY (2010) RNA interference by nanofiber-based siRNA delivery system. J Control Release 144(2):203–212. Available online at http://www.sciencedirect.com/science/article/pii/S0168365910001094
Cohen MM Jr (2002) Bone morphogenetic proteins with some comments on fibrodysplasia ossificans progressiva and NOGGIN. Am J Med Genet 109(2):87–92. doi:10.1002/ajmg.10289
Corey DR (2007) Chemical modification: the key to clinical application of RNA interference? J Clin Invest 117(12):3615–3622. doi:10.1172/JCI33483
Cui Z-K, Fan J, Kim S, Bezouglaia O, Fartash A, Wu BM et al (2015) Delivery of siRNA via cationic Sterosomes to enhance osteogenic differentiation of mesenchymal stem cells. J Control Release 217:42–52. doi:10.1016/j.jconrel.2015.08.031
Deng Y, Zhou H, Zou D, Xie Q, Bi X, Gu P, Fan X (2013) The role of miR-31-modified adipose tissue-derived stem cells in repairing rat critical-sized calvarial defects. Biomaterials 34(28):6717–6728. doi:10.1016/j.biomaterials.2013.05.042
Deng Y, Zhou H, Gu P, Fan X (2014) Repair of canine medial orbital bone defects with miR-31-modified bone marrow mesenchymal stem cells. Invest Ophthalmol Vis Sci 55(9):6016–6023. doi:10.1167/iovs.14-14977
Dirin M, Winkler J (2013) Influence of diverse chemical modifications on the ADME characteristics and toxicology of antisense oligonucleotides. Expert Opin Biol Ther 13(6):875–888. doi:10.1517/14712598.2013.774366
Draz MS, Fang BA, Zhang P et al (2014) Nanoparticle-mediated systemic delivery of siRNA for treatment of cancers and viral infections. Theranostics 4(9):872–892. doi:10.7150/thno.9404
Durcan N, Murphy C, Cryan S-A (2008) Inhalable siRNA: potential as a therapeutic agent in the lungs. Mol Pharm 5(4):559–566. doi:10.1021/mp070048k
Elbashir SM, Harborth J, Lendeckel W, Yalcin A, Weber K, Tuschl T (2001) Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature 411(6836):494–498. doi:10.1038/35078107
Ewe A, Schaper A, Barnert S, Schubert R, Temme A, Bakowsky U, Aigner A (2014) Storage stability of optimal liposome-polyethylenimine complexes (lipopolyplexes) for DNA or siRNA delivery. Acta Biomater 10(6):2663–2673. doi:10.1016/j.actbio.2014.02.037
Felgner PL (1987) Lipofection: a highly efficient, lipid-mediated DNA-transfection procedure. Proc Natl Acad Sci USA 84(21):7413–7417. Available online at http://www.pnas.org/content/84/21/7413.abstract
Filion MC, Phillips NC (1997) Toxicity and immunomodulatory activity of liposomal vectors formulated with cationic lipids toward immune effector cells. Biochim Biophys Acta Biomembr 1329(2):345–356. doi:10.1016/S0005-2736(97)00126-0
Fire A, Xu S, Montgomery MK, Kostas SA, Driver SE, Mello CC (1998) Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 391(6669):806–811. doi:10.1038/35888
Fluiter K, Mook ORF, Baas F (2009) The therapeutic potential of LNA-modified siRNAs: reduction of off-target effects by chemical modification of the siRNA sequence. Methods Mol Biol 487:189–203. doi:10.1007/978-1-60327-547-7_9
Forrest ML, Gabrielson N, Pack DW (2005) Cyclodextrin-polyethylenimine conjugates for targeted in vitro gene delivery. Biotechnol Bioeng 89(4):416–423. doi:10.1002/bit.20356
Gekeler V, Gimmnich P, Hofmann H-P, Grebe C, Rommele M, Leja A et al (2006) G3139 and other CpG-containing immunostimulatory phosphorothioate oligodeoxynucleotides are potent suppressors of the growth of human tumor xenografts in nude mice. Oligonucleotides 16(1):83–93. doi:10.1089/oli.2006.16.83
Gutsch D, Appelhans D, Höbel S, Voit B, Aigner A (2013) Biocompatibility and efficacy of oligomaltose-grafted poly(ethylene imine)s (OM-PEIs) for in vivo gene delivery. Mol Pharm 10(12):4666–4675. doi:10.1021/mp400479g
Hartmann H, Hossfeld S, Schlosshauer B, Mittnacht U, Pêgo AP, Dauner M et al (2013) Hyaluronic acid/chitosan multilayer coatings on neuronal implants for localized delivery of siRNA nanoplexes. J Control Release 168(3):289–297. doi:10.1016/j.jconrel.2013.03.026
Höbel S, Aigner A (2013) Polyethylenimines for siRNA and miRNA delivery in vivo. Wiley Interdiscip Rev Nanomed Nanobiotechnol 5(5):484–501. doi:10.1002/wnan.1228
Höbel S, Koburger I, John M, Czubayko F, Hadwiger P, Vornlocher H-P, Aigner A (2010) Polyethylenimine/small interfering RNA-mediated knockdown of vascular endothelial growth factor in vivo exerts anti-tumor effects synergistically with Bevacizumab. J Gene Med 12(3):287–300. doi:10.1002/jgm.1431
Höbel S, Vornicescu D, Bauer M, Fischer D, Keusgen M, Aigner A (2014) A novel method for the assessment of targeted PEI-based nanoparticle binding based on a static surface plasmon resonance system. Anal Chem 86(14):6827–6835. doi:10.1021/ac402001q
Hossfeld S, Nolte A, Hartmann H, Recke M, Schaller M, Walker T et al (2013) Bioactive coronary stent coating based on layer-by-layer technology for siRNA release. Acta Biomater 9(5):6741–6752. doi:10.1016/j.actbio.2013.01.013
Hoyer J, Neundorf I (2012) Peptide vectors for the nonviral delivery of nucleic acids. Acc Chem Res 45(7):1048–1056. doi:10.1021/ar2002304
Islam MA, Park T-E, Singh B, Maharjan S, Firdous J, Cho M-H et al (2014) Major degradable polycations as carriers for DNA and siRNA. J Control Release 193:74–89. doi:10.1016/j.jconrel.2014.05.055
Jacobson GB, Gonzalez-Gonzalez E, Spitler R, Shinde R, Leake D, Kaspar RL et al (2010) Biodegradable nanoparticles with sustained release of functional siRNA in skin. J Pharm Sci 99(10):4261–4266. doi:10.1002/jps.22147
Jensen DK, Jensen LB, Koocheki S, Bengtson L, Cun D, Nielsen HM, Foged C (2012) Design of an inhalable dry powder formulation of DOTAP-modified PLGA nanoparticles loaded with siRNA. J Control Release 157(1):141–148. doi:10.1016/j.jconrel.2011.08.011
Jhaveri AM, Torchilin VP (2014) Multifunctional polymeric micelles for delivery of drugs and siRNA. Front Pharmacol 5:77. doi:10.3389/fphar.2014.00077
Jia S, Yang X, Song W, Wang L, Fang K, Hu Z et al (2014) Incorporation of osteogenic and angiogenic small interfering RNAs into chitosan sponge for bone tissue engineering. Int J Nanomed 9:5307–5316. doi:10.2147/IJN.S70457
Kanasty RL, Whitehead KA, Vegas AJ, Anderson DG (2012) Action and reaction: the biological response to siRNA and its delivery vehicles. Mol Ther 20(3):513–524. Available online at http://dx.doi.org/10.1038/mt.2011.294
Kanasty R, Dorkin JR, Vegas A, Anderson D (2013) Delivery materials for siRNA therapeutics. Nat Mater 12(11):967–977. Available online at http://dx.doi.org/10.1038/nmat3765
Kanazawa T, Morisaki K, Suzuki S, Takashima Y (2014) Prolongation of life in rats with malignant glioma by intranasal siRNA/drug codelivery to the brain with cell-penetrating peptide-modified micelles. Mol Pharm 11(5):1471–1478. doi:10.1021/mp400644e
Kling J (2010) Safety signal dampens reception for mipomersen antisense. Nat Biotechnol 28(4):295–297. doi:10.1038/nbt0410-295
Koide M, Kinugawa S, Takahashi N, Udagawa N (2010) Osteoclastic bone resorption induced by innate immune responses. Periodontology 2000 54(1):235–246. doi:10.1111/j.1600-0757.2010.00355.x
Krebs, MD, Alsberg E (2011) Localized, targeted, and sustained siRNA delivery. Chemistry (Weinheim an der Bergstrasse, Germany) 17(11):3054–3062. doi:10.1002/chem.201003144
Kwong FNK, Richardson SM, Evans CH (2008) Chordin knockdown enhances the osteogenic differentiation of human mesenchymal stem cells. Arthritis Res Ther 10(3):R65. doi:10.1186/ar2436
Lam JK-W, Liang W, Chan H-K (2012) Pulmonary delivery of therapeutic siRNA. Adv Drug Deliv Rev 64(1):1–15. doi:10.1016/j.addr.2011.02.006
Lappalainen K, Jääskeläinen I, Syrjänen K, Urtti A, Syrjänen S (1994) Comparison of cell proliferation and toxicity assays using two cationic liposomes. Pharm Res 11(8):1127–1131. doi:10.1023/A:1018932714745
Levi B, Nelson ER, Hyun JS, Glotzbach JP, Li S, Nauta A et al (2012) Enhancement of human adipose-derived stromal cell angiogenesis through knockdown of a BMP-2 inhibitor. Plast Reconstr Surg 129(1):53–66. doi:10.1097/PRS.0b013e3182361ff5
Li Y, Fan L, Liu S, Liu W, Zhang H, Zhou T et al (2013) The promotion of bone regeneration through positive regulation of angiogenic–osteogenic coupling using microRNA-26a. Biomaterials 34(21):5048–5058. doi:10.1016/j.biomaterials.2013.03.052
López-Fraga M, Martínez T, Jiménez A (2009) RNA interference technologies and therapeutics: from basic research to products. BioDrugs Clin Immunother Biopharm Gene Ther 23(5):305–332. doi:10.2165/11318190-000000000-00000
Luzi E, Marini F, Sala SC, Tognarini I, Galli G, Brandi ML (2008) Osteogenic differentiation of human adipose tissue-derived stem cells is modulated by the miR-26a targeting of the SMAD1 transcription factor. J Bone Miner Res 23(2):287–295. doi:10.1359/jbmr.071011
Ma Z, Yang C, Song W, Wang Q, Kjems J, Gao S (2014) Chitosan hydrogel as siRNA vector for prolonged gene silencing. J Nanobiotechnol 12:23. doi:10.1186/1477-3155-12-23
Malek A, Czubayko F, Aigner A (2008) PEG grafting of polyethylenimine (PEI) exerts different effects on DNA transfection and siRNA-induced gene targeting efficacy. J Drug Target 16(2):124–139. doi:10.1080/10611860701849058
Manaka T, Suzuki A, Takayama K, Imai Y, Nakamura H, Takaoka K (2011) Local delivery of siRNA using a biodegradable polymer application to enhance BMP-induced bone formation. Biomaterials 32(36):9642–9648. doi:10.1016/j.biomaterials.2011.08.026
Manoharan M (1999) 2′-carbohydrate modifications in antisense oligonucleotide therapy: importance of conformation, configuration and conjugation. Biochim Biophys Acta 1489(1):117–130
Marchini J, Howie B (2010) Genotype imputation for genome-wide association studies. Nat Rev Genet 11(7):499–511. doi:10.1038/nrg2796
Merkel OM, Kissel T (2014) Quo vadis polyplex? J Control Release 190:415–423. doi:10.1016/j.jconrel.2014.06.009
Minakuchi Y, Takeshita F, Kosaka N, Sasaki H, Yamamoto Y, Kouno M et al (2004) Atelocollagen-mediated synthetic small interfering RNA delivery for effective gene silencing in vitro and in vivo. Nucleic Acids Res 32(13):e109. doi:10.1093/nar/gnh093
Mittnacht U, Hartmann H, Hein S, Oliveira H, Dong M, Pêgo AP et al (2010) Chitosan/siRNA nanoparticles biofunctionalize nerve implants and enable neurite outgrowth. Nano Lett 10(10):3933–3939. doi:10.1021/nl1016909
Monaghan M, Browne S, Schenke-Layland K, Pandit A (2014) A collagen-based scaffold delivering exogenous microrna-29B to modulate extracellular matrix remodeling. Mol Ther 22(4):786–796. doi:10.1038/mt.2013.288
Moore Chris B, Guthrie Elizabeth H, Huang MT-H, Taxman Debra J (2010) Short hairpin RNA (shRNA): design, delivery, and assessment of gene knockdown. Methods Mol Biol 629:141–158. doi:10.1007/978-1-60761-657-3_10
Nelson CE, Gupta MK, Adolph EJ, Shannon JM, Guelcher SA, Duvall CL (2012) Sustained local delivery of siRNA from an injectable scaffold. Biomaterials 33(4):1154–1161. doi:10.1016/j.biomaterials.2011.10.033
Nelson CE, Gupta MK, Adolph EJ, Guelcher SA, Duvall CL (2013) siRNA delivery from an injectable scaffold for wound therapy. Adv Wound Care 2(3):93–99. doi:10.1089/wound.2011.0327
Nelson CE, Kim AJ, Adolph EJ, Gupta MK, Yu F, Hocking KM et al (2014) Biomedical applications: tunable delivery of siRNA from a biodegradable scaffold to promote angiogenesis in vivo. Adv Mater 26(4):506. doi:10.1002/adma.201470023
Nguyen MK, Jeon O, Krebs MD, Schapira D, Alsberg E (2014) Sustained localized presentation of RNA interfering molecules from in situ forming hydrogels to guide stem cell osteogenic differentiation. Biomaterials 35(24):6278–6286. doi:10.1016/j.biomaterials.2014.04.048
Novina CD, Sharp PA (2004) The RNAi revolution. Nature 430(6996):161–164. doi:10.1038/430161a
Pan M, Ni J, He H, Gao S, Duan X (2015) New paradigms on siRNA local application. BMB Rep 48(3):147–152. doi:10.5483/BMBRep.2015.48.3.089
Pantazis P, Dimas K, Wyche JH, Anant S, Houchen CW, Panyam J, Ramanujam RP (2012) Preparation of siRNA-encapsulated PLGA nanoparticles for sustained release of siRNA and evaluation of encapsulation efficiency. Methods Mol Biol 906:311–319. doi:10.1007/978-1-61779-953-2_25
Perrier-Groult E, Pasdeloup M, Malbouyres M, Galéra P, Mallein-Gerin F (2013) Control of collagen production in mouse chondrocytes by using a combination of bone morphogenetic protein-2 and small interfering RNA targeting Col1a1 for hydrogel-based tissue-engineered cartilage. Tissue Eng Part C Methods 19(8):652–664. doi:10.1089/ten.TEC.2012.0396
Pisano M, Baldinu P, Sini MC, Ascierto PA, Tanda F, Palmieri G (2008) Targeting Bcl-2 protein in treatment of melanoma still requires further clarifications. Ann Oncol 19(12):2092–2093. doi:10.1093/annonc/mdn672
Polach KJ, Matar M, Rice J, Slobodkin G, Sparks J, Congo R et al (2012) Delivery of siRNA to the mouse lung via a functionalized lipopolyamine. Mol Ther 20(1):91–100. doi:10.1038/mt.2011.210
Prakash TP, Kawasaki AM, Wancewicz EV, Shen L, Monia BP, Ross BS et al (2008) Comparing in vitro and in vivo activity of 2′-O-[2-(methylamino)-2-oxoethyl]- and 2′-O-methoxyethyl-modified antisense oligonucleotides. J Med Chem 51(9):2766–2776. doi:10.1021/jm701537z
Qureshi AT, Monroe WT, Dasa V, Gimble JM, Hayes DJ (2013) miR-148b–nanoparticle conjugates for light mediated osteogenesis of human adipose stromal/stem cells. Biomaterials 34(31):7799–7810. doi:10.1016/j.biomaterials.2013.07.004
Qureshi AT, Doyle A, Chen C, Coulon D, Dasa V, Del Piero F et al (2015) Photoactivated miR-148b-nanoparticle conjugates improve closure of critical size mouse calvarial defects. Acta Biomater 12:166–173. doi:10.1016/j.actbio.2014.10.010
Rujitanaroj P-o, Wang Y-C, Wang J, Chew SY (2011) Nanofiber-mediated controlled release of siRNA complexes for long term gene-silencing applications. Biomaterials 32(25):5915–5923. doi:10.1016/j.biomaterials.2011.04.065
Saito N, Okada T, Horiuchi H, Murakami N, Takahashi J, Nawata M et al (2001) A biodegradable polymer as a cytokine delivery system for inducing bone formation. Nat Biotechnol 19(4):332–335. doi:10.1038/86715
Schäfer J, Höbel S, Bakowsky U, Aigner A (2010) Liposome–polyethylenimine complexes for enhanced DNA and siRNA delivery. Biomaterials 31(26):6892–6900. doi:10.1016/j.biomaterials.2010.05.043
Scheicher B, Schachner-Nedherer A-L, Zimmer A (2015) Protamine-oligonucleotide-nanoparticles: recent advances in drug delivery and drug targeting. Eur J Pharm Sci 75:54–59. doi:10.1016/j.ejps.2015.04.009
Schneider H, Sedaghati B, Naumann A, Hacker MC, Schulz-Siegmund M (2014) Gene silencing of chordin improves BMP-2 effects on osteogenic differentiation of human adipose tissue-derived stromal cells. Tissue Eng A 20(1–2):335–345. doi:10.1089/ten.TEA.2012.0563
Song W, Song X, Yang C, Gao S, Klausen LH, Zhang Y et al (2015) Chitosan/siRNA functionalized titanium surface via a layer-by-layer approach for in vitro sustained gene silencing and osteogenic promotion. Int J Nanomedicine 10:2335–2346. doi:10.2147/IJN.S76513
Stessl M, Noe CR, Winkler J (2012) Off-target effects and safety aspects of phosphorothioate oligonucleotides. In: Erdmann VA, Jan B (eds) From nucleic acids sequences to molecular medicine. Springer, Berlin/Heidelberg, pp 67–83
Summerton J (1999) Morpholino antisense oligomers: the case for an RNase H-independent structural type. Biochimica et Biophysica Acta 1489(1):141–158. doi:10.1016/S0167-4781(99)00150-5
Summerton JE (2007) Morpholino, siRNA, and S-DNA compared: impact of structure and mechanism of action on off-target effects and sequence specificity. Curr Top Med Chem 7(7):651–660
Tabernero J, Shapiro GI, LoRusso PM et al (2013) First-in-humans trial of an RNA interference therapeutic targeting VEGF and KSP in cancer patients with liver involvement. Cancer Dis 3(4):406–417. doi:10.1158/2159-8290.CD-12-0429
Takayama K, Suzuki A, Manaka T, Taguchi S, Hashimoto Y, Imai Y et al (2009) RNA interference for noggin enhances the biological activity of bone morphogenetic proteins in vivo and in vitro. J Bone Miner Metab 27(4):402–411. doi:10.1007/s00774-009-0054-x
Tebes SJ, Kruk PA (2005) The genesis of RNA interference, its potential clinical applications, and implications in gynecologic cancer. Gynecol Oncol 99(3):736–741. doi:10.1016/j.ygyno.2005.08.031
Wang Y, Grainger DW (2010) siRNA knock-down of RANK signaling to control osteoclast-mediated bone resorption. Pharm Res 27(7):1273–1284. doi:10.1007/s11095-010-0099-5
Wang D, Robinson DR, Kwon GS, Samuel J (1999) Encapsulation of plasmid DNA in biodegradable poly(d, l-lactic-co-glycolic acid) microspheres as a novel approach for immunogene delivery. J Control Release 57(1):9–18. doi:10.1016/S0168-3659(98)00099-6
Wang Y, Tran KK, Shen H, Grainger DW (2012) Selective local delivery of RANK siRNA to bone phagocytes using bone augmentation biomaterials. Biomaterials 33(33):8540–8547. doi:10.1016/j.biomaterials.2012.07.039
Watts JK, Corey DR (2010) Clinical status of duplex RNA. Bioorg Med Chem Lett 20(11):3203–3207. doi:10.1016/j.bmcl.2010.03.109
Werth S, Urban-Klein B, Dai L, Hobel S, Grzelinski M, Bakowsky U et al (2006) A low molecular weight fraction of polyethylenimine (PEI) displays increased transfection efficiency of DNA and siRNA in fresh or lyophilized complexes. J Control Release 112(2):257–270. doi:10.1016/j.jconrel.2006.02.009
Winkler J, Stessl M, Amartey J, Noe CR (2010) Off-target effects related to the phosphorothioate modification of nucleic acids. ChemMedChem 5(8):1344–1352. doi:10.1002/cmdc.201000156
Wozney JM (1992) The bone morphogenetic protein family and osteogenesis. Mol Reprod Dev 32(2):160–167. doi:10.1002/mrd.1080320212
Xu L, Anchordoquy T (2011) Drug delivery trends in clinical trials and translational medicine: challenges and opportunities in the delivery of nucleic acid-based therapeutics. J Pharm Sci 100(1):38–52. doi:10.1002/jps.22243
Yamamoto T, Nakatani M, Narukawa K, Obika S (2011) Antisense drug discovery and development. Future Med Chem 3(3):339–365. doi:10.4155/fmc.11.2
Yanagita M (2005) BMP antagonists: their roles in development and involvement in pathophysiology. Bone Morphog Proteins 16(3):309–317. doi:10.1016/j.cytogfr.2005.02.007
Yu RZ, Zhang H, Geary RS, Graham M, Masarjian L, Lemonidis K et al (2001) Pharmacokinetics and pharmacodynamics of an antisense phosphorothioate oligonucleotide targeting Fas mRNA in mice. J Pharmacol Exp Ther 296(2):388–395
Yu RZ, Lemonidis KM, Graham MJ, Matson JE, Crooke RM, Tribble DL et al (2009) Cross-species comparison of in vivo PK/PD relationships for second-generation antisense oligonucleotides targeting apolipoprotein B-100. Biochem Pharmacol 77(5):910–919. doi:10.1016/j.bcp.2008.11.005
Zhang X, Kovtun A, Mendoza-Palomares C, Oulad-Abdelghani M, Fioretti F, Rinckenbach S et al (2010) SiRNA-loaded multi-shell nanoparticles incorporated into a multilayered film as a reservoir for gene silencing. Biomaterials 31(23):6013–6018. doi:10.1016/j.biomaterials.2010.04.024
Zhang G, Guo B, Wu H, Tang T, Zhang B-T, Zheng L et al (2012) A delivery system targeting bone formation surfaces to facilitate RNAi-based anabolic therapy. Nat Med 18(2):307–314. doi:10.1038/nm.2617
Zhao R, Yan Q, Huang H, Lv J, Ma W (2013) Transdermal siRNA-TGFβ1-337 patch for hypertrophic scar treatment. Matrix Biol 32(5):265–276. doi:10.1016/j.matbio.2013.02.004
Zhou J, Rossi JJ (2014) Cell-type-specific, aptamer-functionalized agents for targeted disease therapy. Mol Ther Nucleic Acid 3:e169. doi:10.1038/mtna.2014.21
Zhu L, Mahato RI (2010) Targeted delivery of siRNA to hepatocytes and hepatic stellate cells by bioconjugation. Bioconjug Chem 21(11):2119–2127. doi:10.1021/bc100346n
Zimmermann TS, Lee ACH, Akinc A et al (2006) RNAi-mediated gene silencing in non-human primates. Nature 441(7089):111–114. doi:10.1038/nature04688
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2016 Springer International Publishing Switzerland
About this chapter
Cite this chapter
Sedaghati, B., Hoyer, J., Aigner, A., Hacker, M.C., Schulz-Siegmund, M. (2016). Controlled Release Technologies for RNAi Strategies in Regenerative Medicine. In: Steinhoff, G. (eds) Regenerative Medicine - from Protocol to Patient. Springer, Cham. https://doi.org/10.1007/978-3-319-28274-9_8
Download citation
DOI: https://doi.org/10.1007/978-3-319-28274-9_8
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-28272-5
Online ISBN: 978-3-319-28274-9
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)