Peptide carriers as delivery vehicles for therapeutic nucleic acids. Мechanisms and potential applications in medicine

Cover Page

Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription Access

Abstract

Currently, a significant number of drugs based on therapeutic nucleic acids are being under development for the treatment of oncological, inflammatory, infectious diseases, and metabolic disorders. A growing number of approved nucleic acid therapeutics demonstrate the potential of gene therapy approaches. Therapeutic nucleic acids realize their biological effect in the cytoplasm, while plasma membrane is the main barrier to their intracellular delivery. Therefore, specially designed carriers are often used during the development of such drugs. The optimal carrier should not only facilitate the internalization of nucleic acids, but also exhibit no toxic effects, provide stabilization, and must be suitable for large scale production at low cost. Cell penetrating peptides (CPPs) match all these requirements. CPPs are effective and low-toxic carriers of nucleic acids. They usually represent basic peptides with a positive charge at physiological pH that capable to form nanostructures with negatively charged nucleic acids. Numerous preclinical studies in which CPP has been used as a carrier have shown promising results. In some cases, CPP-containing drugs successfully passed through clinical trials and the implemented into clinical practice. In this review, we consider the variety of therapeutic nucleic acids and summarize the experience of using CPP for their intracellular delivery. In addition, the classification and mechanisms of CPP cellular uptake are discussed, the understanding of which will accelerate the development of new gene therapy drugs.

About the authors

E. D Timotievich

Institute of Immunology, National Research Center, Federal Medical-Biological Agency of Russia

Email: ed0594@yandex.ru
115522 Moscow, Russia

I. P Shilovskiy

Institute of Immunology, National Research Center, Federal Medical-Biological Agency of Russia

115522 Moscow, Russia

M. R Khaitov

Institute of Immunology, National Research Center, Federal Medical-Biological Agency of Russia

115522 Moscow, Russia

References

  1. Chaudhary, N., Weissman, D., and Whitehead, K. A. (2021) mRNA vaccines for infectious diseases: principles, delivery and clinical translation, Nat. Rev. Drug Discov., 20, 817-838, doi: 10.1038/S41573-021-00283-5.
  2. Kulkarni, J. A., Witzigmann, D., Thomson, S. B., Chen, S., Leavitt, B. R., Cullis, P. R., and van der Meel, R. (2021) The current landscape of nucleic acid therapeutics, Nat. Nanotechnol., 16, 630-643, doi: 10.1038/s41565-021-00898-0.
  3. Talap, J., Zhao, J., Shen, M., Song, Z., Zhou, H., Kang, Y., Sun, L., Yu, L., Zeng, S., and Cai, S. (2021) Recent advances in therapeutic nucleic acids and their analytical methods, J. Pharm. Biomed. Anal., 206, 114368, doi: 10.1016/J.JPBA.2021.114368.
  4. Wang, Y., Zhang, R., Tang, L., and Yang, L. (2022) Nonviral delivery systems of mRNA vaccines for cancer gene therapy, Pharmaceutics, 14, 512, doi: 10.3390/PHARMACEUTICS14030512.
  5. Shirley, J. L., de Jong, Y. P., Terhorst, C., and Herzog, R. W. (2020) Immune responses to viral gene therapy vectors, Mol. Ther., 28, 709-722, doi: 10.1016/J.YMTHE.2020.01.001.
  6. Yan, Y., Liu, X. Y., Lu, A., Wang, X. Y., Jiang, L. X., and Wang, J. C. (2022) Non-viral vectors for RNA delivery, J. Control. Rel., 342, 241, doi: 10.1016/J.JCONREL.2022.01.008.
  7. Zou, Z., Shen, Q., Pang, Y., Li, X., Chen, Y., Wang, X., Luo, X., Wu, Z., Bao, Z., Zhang, J., Liang, J., Kong, L., Yan, L., Xiong, L., Zhu, T., Yuan, S., Wang, M., Cai, K., Yao, Y., Wu, J., Jiang, Y., Liu, H., Liu, J., Zhou, Y., Dong, Q., Wang, W., Zhu, K., Li, L., Lou, Y., Wang, H., Li, Y., and Lin, H. (2019) The synthesized transporter K16APoE enabled the therapeutic HAYED peptide to cross the blood-brain barrier and remove excess iron and radicals in the brain, thus easing Alzheimer's disease, Drug Deliv. Transl. Res., 9, 394-403, doi: 10.1007/s13346-018-0579-4.
  8. Matijass, M., and Neundorf, I. (2021) Cell-penetrating peptides as part of therapeutics used in cancer research, Med. Drug Discov., 10, 100092, doi: 10.1016/j.medidd.2021.100092.
  9. Derakhshankhah, H., and Jafari, S. (2018) Cell penetrating peptides: a concise review with emphasis on biomedical applications, Biomed. Pharmacother., 108, 1090-1096, doi: 10.1016/j.biopha.2018.09.097.
  10. Kang, Y. C., Son, M., Kang, S., Im, S., Piao, Y., Lim, K. S., Song, M. Y., Park, K. S., Kim, Y. H., and Pak, Y. K. (2018) Cell-penetrating artificial mitochondria-targeting peptide-conjugated metallothionein 1A alleviates mitochondrial damage in Parkinson's disease models, Exp. Mol. Med., 50, 1-13, doi: 10.1038/s12276-018-0124-z.
  11. Xie, J., Bi, Y., Zhang, H., Dong, S., Teng, L., Lee, R. J., and Yang, Z. (2020) Cell-penetrating peptides in diagnosis and treatment of human diseases: from preclinical research to clinical application, Front. Pharmacol., 11, 697, doi: 10.3389/fphar.2020.00697.
  12. Lopuszynski, J., Agrawal, V., and Zahid, M. (2022) Tissue-specific cell penetrating peptides for targeted delivery of small interfering RNAs, Med. Res. Arch., doi: 10.18103/mra.v10i8.2998.
  13. Nh�n, N. T. T., Maidana, D. E., and Yamada, K. H. (2023) Ocular delivery of therapeutic agents by cell-penetrating peptides, Cells, 12, 1071, doi: 10.3390/cells12071071.
  14. Zorko, M., Jones, S., and Langel, �. (2022) Cell-penetrating peptides in protein mimicry and cancer therapeutics, Adv. Drug Deliv. Rev., 180, 114044, doi: 10.1016/J.ADDR.2021.114044.
  15. Jiang, J. (2021) Cell-penetrating peptide-mediated nanovaccine delivery, Curr. Drug Targets, 22, 896-912, doi: 10.2174/1389450122666210203193225.
  16. Delcroix, M., and Riley, L. W. (2010) Cell-penetrating peptides for antiviral drug development, Pharmaceuticals, 3, 448-470, doi: 10.3390/ph3030448.
  17. Khaitov, M., Nikonova, A., Kofiadi, I., Shilovskiy, I., Smirnov, V., Elisytina, O., Maerle, A., Shatilov, A., Shatilova, A., Andreev, S., Sergeev, I., Trofimov, D., Latysheva, T., Ilyna, N., Martynov, A., Rabdano, S., Ruzanova, E., Savelev, N., Pletiukhina, I., Safi, A., Ratnikov, V., Gorelov, V., Kaschenko, V., Kucherenko, N., Umarova, I., Moskaleva, S., Fabrichnikov, S., Zuev, O., Pavlov, N., Kruchko, D., Berzin, I., Goryachev, D., Merkulov, V., Shipulin, G., Udin, S., Trukhin, V., Valenta, R., and Skvortsova, V. (2023) Treatment of COVID-19 patients with a SARS-CoV-2-specific siRNA-peptide dendrimer formulation, Allergy, 78, 1639-1653, doi: 10.1111/ALL.15663.
  18. Sridharan, K., and Gogtay, N. J. (2016) Therapeutic nucleic acids: current clinical status, Br. J. Clin. Pharmacol., 82, 659-672, doi: 10.1111/BCP.12987.
  19. Davies-Sala, C., Soler-Bistu�, A., Bonomo, R. A., Zorreguieta, A., and Tolmasky, M. E. (2015) External guide sequence technology: a path to development of novel antimicrobial therapeutics, Ann. N. Y. Acad. Sci., 1354, 98-110, doi: 10.1111/NYAS.12755.
  20. Gadgil, H., and Jarrett, H. W. (2002) Oligonucleotide trapping method for purification of transcription factors, J. Chromatogr. A, 966, 99-110, doi: 10.1016/s0021-9673(02)00738-0.
  21. Vickers, T. A., Sabripour, M., and Crooke, S. T. (2011) U1 adaptors result in reduction of multiple pre-mRNA species principally by sequestering U1snRNP, Nucleic Acids Res., 39, e71, doi: 10.1093/NAR/GKR150.
  22. Agrawal, N., Dasaradhi, P. V. N., Mohmmed, A., Malhotra, P., Bhatnagar, R. K., and Mukherjee, S. K. (2003) RNA interference: biology, mechanism, and applications, Microbiol. Mol. Biol. Rev., 67, 657, doi: 10.1128/MMBR.67.4.657-685.2003.
  23. Hammond, S. M., Boettcher, S., Caudy, A. A., Kobayashi, R., and Hannon, G. J. (2001) Argonaute 2, a link between genetic and biochemical analyses of RNAi, Science, 293, 1146-1150, doi: 10.1126/science.1064023.
  24. Gangopadhyay, S., and Gore, K. R. (2022) Advances in siRNA therapeutics and synergistic effect on siRNA activity using emerging dual ribose modifications, RNA Biol., 19, 452-467, doi: 10.1080/15476286.2022.2052641.
  25. Wan-Hin Hui, R., Mak, L. Y., Seto, W. K., and Yuen, M. F. (2022) RNA interference as a novel treatment strategy for chronic hepatitis B infection, Clin. Mol. Hepatol., 28, 408, doi: 10.3350/CMH.2022.0012.
  26. Ray, K. K., Wright, R. S., Kallend, D., Koenig, W., Leiter, L. A., Raal, F. J., Bisch, J. A., Richardson, T., Jaros, M., Wijngaard, P. L. J., and Kastelein, J. J. P. (2020) Two phase 3 trials of inclisiran in patients with elevated LDL cholesterol, New Eng. J. Med., 382, 1507-1519, doi: 10.1056/nejmoa1912387.
  27. Zhang, M. M., Bahal, R., Rasmussen, T. P., Manautou, J. E., and Zhong, X.-Bo (2021) The growth of siRNA-based therapeutics: updated clinical studies, Biochem. Pharmacol., 189, 114432, doi: 10.1016/J.BCP.2021.114432.
  28. Khaitov, M., Nikonova, A., Shilovskiy, I., Kozhikhova, K., Kofiadi, I., Vishnyakova, L., Nikolskii, A., Gattinger, P., Kovchina, V., Barvinskaia, E., Yumashev, K., Smirnov, V., Maerle, A., Kozlov, I., Shatilov, A., Timofeeva, A., Andreev, S., Koloskova, O., Kuznetsova, N., Vasina, D., Nikiforova, M., Rybalkin, S., Sergeev, I., Trofimov, D., Martynov, A., Berzin, I., Gushchin, V., Kovalchuk, A., Borisevich, S., Valenta, R., Khaitov, R., and Skvortsova, V. (2021) Silencing of SARS-CoV-2 with modified siRNA-peptide dendrimer formulation, Allergy, 76, 2840-2854, doi: 10.1111/all.14850.
  29. Pardi, N., Hogan, M. J., and Weissman, D. (2020) Recent advances in mRNA vaccine technology, Curr. Opin. Immunol., 65, 14-20, doi: 10.1016/J.COI.2020.01.008.
  30. Ledford, H. (2020) Moderna COVID vaccine becomes second to get US authorization, Nature, doi: 10.1038/D41586-020-03593-7.
  31. Blind, J. E., McLeod, E. N., Brown, A., Patel, H., and Ghosh, S. (2020) Biosafety practices for in vivo viral-mediated gene therapy in the health care setting, Appl. Biosaf., 25, 194, doi: 10.1177/1535676020942195.
  32. Roberts, T. C., Langer, R., and Wood, M. J. A. (2020) Advances in oligonucleotide drug delivery, Nat. Rev. Drug Discov., 19, 673, doi: 10.1038/S41573-020-0075-7.
  33. Chen, H., Ren, X., Xu, S., Zhang, D., and Han, T. (2022) Optimization of lipid nanoformulations for effective mRNA delivery, Int. J. Nanomed., 17, 2893-2905, doi: 10.2147/IJN.S363990.
  34. Paunovska, K., Loughrey, D., and Dahlman, J. E. (2022) Drug delivery systems for RNA therapeutics, Nat. Rev. Genet., 23, 265, doi: 10.1038/S41576-021-00439-4.
  35. Khan, M. M., Filipczak, N., and Torchilin, V. P. (2021) Cell penetrating peptides: A versatile vector for co-delivery of drug and genes in cancer, J. Controll. Rel., 330, 1220-1228, doi: 10.1016/j.jconrel.2020.11.028.
  36. Taylor, R. E., and Zahid, M. (2020) Cell penetrating peptides, novel vectors for gene therapy, Pharmaceutics, 12, 225, doi: 10.3390/pharmaceutics12030225.
  37. Falato, L., Gestin, M., and Langel, �. (2021) Cell-penetrating peptides delivering siRNAs: An overview, Methods Mol. Biol., 2282, 329-352, doi: 10.1007/978-1-0716-1298-9_18.
  38. R�dis-Baptista, G. (2021) Cell-penetrating peptides derived from animal venoms and toxins, Toxins (Basel), 13, 147, doi: 10.3390/toxins13020147.
  39. Zorko, M., and Langel, �. (2022) Cell-penetrating peptides, Methods Mol. Biol., 2383, 3-32, doi: 10.1007/978-1-0716-1752-6_1.
  40. Ruseska, I., and Zimmer, A. (2020) Internalization mechanisms of cell-penetrating peptides, Beilstein J. Nanotechnol., 11, 101-123, doi: 10.3762/bjnano.11.10.
  41. Holm, T., Andaloussi, S. El, and Langel, �. (2011) Comparison of CPP uptake methods, Methods Mol. Biol., 683, 207-217, doi: 10.1007/978-1-60761-919-2_15.
  42. Li, Z., Zhang, Y., Zhu, D., Li, S., Yu, X., Zhao, Y., Ouyang, X., Xie, Z., and Li, L. (2017) Transporting carriers for intracellular targeting delivery via non-endocytic uptake pathways, Drug Deliv., 24, 45-55, doi: 10.1080/10717544.2017.1391889.
  43. Sadeghian, I., Heidari, R., Sadeghian, S., Raee, M. J., and Negahdaripour, M. (2022) Potential of cell-penetrating peptides (CPPs) in delivery of antiviral therapeutics and vaccines, Eur. J. Pharm. Sci., 169, 106094, doi: 10.1016/J.EJPS.2021.106094.
  44. Trabulo, S., Cardoso, A. L., Mano, M., and de Lima, M. C. P. (2010) Cell-penetrating peptides - mechanisms of cellular uptake and generation of delivery systems, Pharmaceuticals, 3, 961-993, doi: 10.3390/PH3040961.
  45. Nath, A. (2021) Prediction for understanding the effectiveness of antiviral peptides, Comput. Biol. Chem., 95, 107588, doi: 10.1016/j.compbiolchem.2021.107588.
  46. Kaksonen, M., and Roux, A. (2018) Mechanisms of clathrin-mediated endocytosis, Nat. Rev. Mol. Cell Biol., 19, 313-326, doi: 10.1038/NRM.2017.132.
  47. Kawaguchi, Y., Takeuchi, T., Kuwata, K., Chiba, J., Hatanaka, Y., Nakase, I., and Futaki, S. (2016) Syndecan-4 is a receptor for clathrin-mediated endocytosis of arginine-rich cell-penetrating peptides, Bioconjug. Chem., 27, 1119-1130, doi: 10.1021/ACS.BIOCONJCHEM.6B00082.
  48. Futaki, S., and Nakase, I. (2017) Cell-surface interactions on arginine-rich cell-penetrating peptides allow for multiplex modes of internalization, Acc. Chem. Res., 50, 2449-2456, doi: 10.1021/ACS.ACCOUNTS.7B00221.
  49. Pujals, S., and Giralt, E. (2008) Proline-rich, amphipathic cell-penetrating peptides, Adv. Drug Deliv. Rev., 60, 473-484, doi: 10.1016/J.ADDR.2007.09.012.
  50. S��lik, P., Padari, K., Niinep, A., Lorents, A., Hansen, M., Jokitalo, E., Langel, �., and Pooga, M. (2009) Protein delivery with transportans is mediated by caveolae rather than flotillin-dependent pathways, Bioconjug. Chem., 20, 877-887, doi: 10.1021/BC800416F.
  51. Taylor, B. N., Mehta, R. R., Yamada, T., Lekmine, F., Christov, K., Chakrabarty, A. M., Green, A., Bratescu, L., Shilkaitis, A., Beattie, C. W., and das Gupta, T. K. (2009) Noncationic peptides obtained from azurin preferentially enter cancer cells, Cancer Res., 69, 537-546, doi: 10.1158/0008-5472.can-08-2932.
  52. Ye, J., Pei, X., Cui, H., Yu, Z., Lee, H., Wang, J., Wang, X., Sun, L., He, H., and Yang, V. C. (2018) Cellular uptake mechanism and comparative in vitro cytotoxicity studies of monomeric LMWP-siRNA conjugate, J. Industr. Engineer. Chem., 63, 103-111, doi: 10.1016/J.JIEC.2018.02.005.
  53. Yang, S. T., Zaitseva, E., Chernomordik, L. V., and Melikov, K. (2010) Cell-penetrating peptide induces leaky fusion of liposomes containing late endosome-specific anionic lipid, Biophys. J., 99, 2525-2533, doi: 10.1016/J.BPJ.2010.08.029.
  54. Cerrato, C. P., and Langel, �. (2022) An update on cell-penetrating peptides with intracellular organelle targeting, Expert Opin. Drug Deliv., 19, 133-146, doi: 10.1080/17425247.2022.2034784.
  55. Wang, H. Y., Chen, J. X., Sun, Y. X., Deng, J. Z., Li, C., Zhang, X. Z., and Zhuo, R. X. (2011) Construction of cell penetrating peptide vectors with N-terminal stearylated nuclear localization signal for targeted delivery of DNA into the cell nuclei, J. Control Rel., 155, 26-33, doi: 10.1016/J.JCONREL.2010.12.009.
  56. Alkhashrom, S., Kicuntod, J., Stillger, K., L�tzenburg, T., Anzenhofer, C., Neundorf, I., Marschall, M., and Eichler, J. (2022) A peptide inhibitor of the human cytomegalovirus core nuclear egress complex, Pharmaceuticals, 15, 1040, doi: 10.3390/PH15091040.
  57. Huang, S., Zhu, Z., Jia, B., Zhang, W., and Song, J. (2021) Design of acid-activated cell-penetrating peptides with nuclear localization capacity for anticancer drug delivery, J. Pept. Sci., 27, e3354, doi: 10.1002/PSC.3354.
  58. Mueller, J., Kretzschmar, I., Volkmer, R., and Boisguerin, P. (2008) Comparison of cellular uptake using 22 CPPs in 4 different cell lines, Bioconjug. Chem., 19, 2363-2374, doi: 10.1021/BC800194E.
  59. Chiu, Y. L., Ali, A., Chu, C. Y., Cao, H., and Rana, T. M. (2004) Visualizing a correlation between siRNA localization, cellular uptake, and RNAi in living cells, Chem. Biol., 11, 1165-1175, doi: 10.1016/j.chembiol.2004.06.006.
  60. Tai, W., and Gao, X. (2017) Functional peptides for siRNA delivery, Adv. Drug Deliv. Rev., 110-111, 157-168, doi: 10.1016/J.ADDR.2016.08.004.
  61. Wang, F., Wang, Y., Zhang, X., Zhang, W., Guo, S., and Jin, F. (2014) Recent progress of cell-penetrating peptides as new carriers for intracellular cargo delivery, J. Control Rel., 174, 126-136, doi: 10.1016/J.JCONREL.2013.11.020.
  62. Guidotti, G., Brambilla, L., and Rossi, D. (2017) Cell-penetrating peptides: from basic research to clinics, Trends Pharmacol. Sci., 38, 406-424, doi: 10.1016/J.TIPS.2017.01.003.
  63. Crombez, L., Morris, M. C., Dufort, S., Aldrian-Herrada, G., Nguyen, Q., Mc Master, G., Coll, J. L., Heitz, F., and Divita, G. (2009) Targeting cyclin B1 through peptide-based delivery of siRNA prevents tumour growth, Nucleic Acids Res., 37, 4559-4569, doi: 10.1093/NAR/GKP451.
  64. Michiue, H., Eguchi, A., Scadeng, M., and Dowdy, S. F. (2009) Induction of in vivo synthetic lethal RNAi responses to treat glioblastoma, Cancer Biol. Ther., 8, 2304-2311, doi: 10.4161/CBT.8.23.10271.
  65. Zeng, Z., Han, S., Hong, W., Lang, Y., Li, F., Liu, Y., Li, Z., Wu, Y., Li, W., Zhang, X., and Cao, Z. (2016) A Tat-conjugated peptide nucleic acid Tat-PNA-DR inhibits hepatitis B virus replication in vitro and in vivo by targeting LTR direct repeats of HBV RNA, Mol. Ther. Nucleic Acids, 5, e295, doi: 10.1038/MTNA.2016.11.
  66. Moerdyk-Schauwecker, M., Stein, D. A., Eide, K., Blouch, R. E., Bildfell, R., Iversen, P., and Jin, L. (2009) Inhibition of HSV-1 ocular infection with morpholino oligomers targeting ICP0 and ICP27, Antiviral Res., 84, 131-141, doi: 10.1016/J.antiviral.2009.07.020.
  67. Mehrlatifan, S., Mirnurollahi, S. M., Motevalli, F., Rahimi, P., Soleymani, S., and Bolhassani, A. (2016) The structural HCV genes delivered by MPG cell penetrating peptide are directed to enhance immune responses in mice model, Drug Deliv., 23, 2852-2859, doi: 10.3109/10717544.2015.1108375.
  68. Moulton, H. M., Fletcher, S., Neuman, B. W., McClorey, G., Stein, D. A., Abes, S., Wilton, S. D., Buchmeier, M. J., Lebleu, B., and Iversen, P. L. (2007) Cell-penetrating peptide-morpholino conjugates alter pre-mRNA splicing of DMD (Duchenne muscular dystrophy) and inhibit murine coronavirus replication in vivo, Biochem. Soc. Trans., 35, 826-828, doi: 10.1042/BST0350826.
  69. Hosseini, A., Lattanzio, F. A., Samudre, S. S., Disandro, G., Sheppard, J. D., and Williams, P. B. (2012) Efficacy of a phosphorodiamidate morpholino oligomer antisense compound in the inhibition of corneal transplant rejection in a rat cornea transplant model, J. Ocul. Pharmacol. Ther., 28, 194-201, doi: 10.1089/JOP.2011.0135.
  70. Zhang, C., Ren, W., Liu, Q., Tan, Z., Li, J., and Tong, C. (2019) Transportan-derived cell-penetrating peptide delivers siRNA to inhibit replication of influenza virus in vivo, Drug Des. Devel. Ther., 13, 1059-1068, doi: 10.2147/DDDT.S195481.
  71. Yuan, J., Stein, D. A., Lim, T., Qiu, D., Coughlin, S., Liu, Z., Wang, Y., Blouch, R., Moulton, H. M., Iversen, P. L., and Yang, D. (2006) Inhibition of Coxsackievirus B3 in cell cultures and in mice by peptide-conjugated morpholino oligomers targeting the internal ribosome entry site, J. Virol., 80, 11510, doi: 10.1128/JVI.00900-06.
  72. Enterlein, S., Warfield, K. L., Swenson, D. L., Stein, D. A., Smith, J. L., Gamble, C. S., Kroeker, A. D., Iversen, P. L., Bavari, S., and M�hlberger, E. (2006) VP35 knockdown inhibits Ebola virus amplification and protects against lethal infection in mice, Antimicrob. Agents Chemother., 50, 984, doi: 10.1128/AAC.50.3.984-993.2006.
  73. Kozhikhova, K. V., Shilovskiy, I. P., Shatilov, A. A., Timofeeva, A. V., Turetskiy, E. A., Vishniakova, L. I., Nikolskii, A. A., Barvinskaya, E. D., Karthikeyan, S., Smirnov, V. V., Kudlay, D. A., Andreev, S. M., and Khaitov, M. R. (2020) Linear and dendrimeric antiviral peptides: design, chemical synthesis and activity against human respiratory syncytial virus, J. Mater. Chem. B, 8, 2607-2617, doi: 10.1039/c9tb02485a.
  74. Shilovskiy, I., Nikonova, A., Barvinskaia, E., Kaganova, M., Nikolskii, A., Vishnyakova, L., Kovchina, V., Yumashev, K., Korneev, A., Petukhova, O., Kudlay, D., Smirnov, V., Andreev, S., Kozhikhova, K., Shatilov, A., Shatilova, A., Maerle, A., Sergeev, I., Trofimov, D., and Khaitov, M. (2022) Anti-inflammatory effect of siRNAs targeted il-4 and il-13 in a mouse model of allergic rhinitis, Allergy, 77, 2829-2832, doi: 10.1111/ALL.15366.
  75. Nikolskii, A. A., Shilovskiy, I. P., Yumashev, K. V., Vishniakova, L. I., Barvinskaia, E. D., Kovchina, V. I., Korneev, A. V., Turenko, V. N., Kaganova, M. M., Brylina, V. E., Nikonova, A. A., Kozlov, I. B., Kofiadi, I. A., Sergeev, I. V., Maerle, A. V., Petukhova, O. A., Kudlay, D. A., and Khaitov, M. R. (2021) Effect of local suppression of Stat3 gene expression in a mouse model of pulmonary neutrophilic inflammation, Immunologiya, 42, 600-614, doi: 10.33029/0206-4952-2021-42-6-600-614.
  76. Shilovskiy, I., Sundukova, M., Korneev, A., Nikolskii, A., Barvinskaya, E., Kovchina, V., Vishniakova, L., Turenko, V., Yumashev, K., Kaganova, M., Brilina, V., Sergeev, I., Maerle, A., Kudlay, D., Petukhova, O., Khaitov, M. (2022) The mixture of siRNAs targeted to IL-4 and IL-13 genes effectively reduces the airway hyperreactivity and allergic inflammation in a mouse model of asthma, Int. Immunopharmacol., 103, 108432, doi: 10.1016/J.INTIMP.2021.108432.
  77. Stiltner, J., McCandless, K., and Zahid, M. (2021) Cell-penetrating peptides: applications in tumor diagnosis and therapeutics, Pharmaceutics, 13, 890, doi: 10.3390/PHARMACEUTICS13060890.
  78. Abes, R., Arzumanov, A. A., Moulton, H. M., Abes, S., Ivanova, G. D., Iversen, P. L., Gait, M. J., and Lebleu, B. (2007) Cell-penetrating-peptide-based delivery of oligonucleotides: an overview, Biochem. Soc. Trans., 35, 775-779, doi: 10.1042/BST0350775.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2023 Russian Academy of Sciences