توسعه و یافتن الیگونوکلئوتیدها برای مارکرهای گلبول قرمز تیپ B با هدف کاربرد در انتقال دارویی

نوع مقاله : مقاله کامل

نویسندگان

1 گروه پاتوبیولوژی، دانشکده دامپزشکی دانشگاه فردوسی مشهد، مشهد، ایران

2 پژوهشکده بیوتکنولوژی، دانشکده دامپزشکی دانشگاه فردوسی مشهد، مشهد، ایران

3 مرکز تحقیقات ایمونولوژی، پژوهشکده علوم پایه، دانشگاه علوم پزشکی مشهد، مشهد، ایران

4 مرکز ژنومیکس مقایسهای، دانشگاه مرداک، پرت 0116 ، استرالیا

چکیده

آپتامرها با جنسی از الیگونوکلئوتید به دلیل توانایی در اتصال به اهداف مختلف با اختصاصیت و ویژگی بسیار بالا، می‌توانند برای انتقال دارو بصورت اختصاصی به ملکول هدف به کار گرفته شوند. پاکسازی سریع کلیوی داروهای بر پایه نوکلئیک‌اسید که توسط عروق خونی منتقل می‌شوند، یکی از مشکلات اساسی برای انتقال این گونه داروها توسط سیستم قلبی عروقی می‌باشد. برای حل این مسئله در این مطالعه یافتن و توسعه آپتامر برای گلبول‌های قرمز خون مبنا قرار گرفت زیرا گلبول‌های قرمز به راحتی در طول سیستم قلبی و عروقی جابجا می‌شوند. گلبول‌های قرمز با دارا بودن ویژگی‌های خاص، گزینه بسیار مناسبی به عنوان انتقال‌دهنده فیزیولوژیک داروها در بدن می‌باشند. بدین منظور با استفاده از گلبول‌های قرمز و هدف قرار دادن 4-O-((2-O-(β-D-fucopyranosyl)-3-O-(α-D-galactopyranosyl))-β-galactopyranosyl)-2-acetamido-2-deoxy-α-D-glucopyranoside در سطح گلبول قرمز سلکس سلولی (Cell-SELEX) انجام شد. بعد از 15 دور از سلکس، با سکانس کردن محصول نهایی، آپتامرهای RNV544 و RNV543 شناسایی گردید که گزینه‌های مناسبی برای هدف قرار دادن گلبول‌های قرمز می‌باشند. میزان اتصال با استفاده از فلوسایتومتری برای RNV544 و RNV543 تایید شد. نتیجه این مطالعه یافتن آپتامرهایی بود که توانایی اتصال اختصاصی به گلبول‌های قرمز تیپ B را دارند.

کلیدواژه‌ها

عنوان مقاله [English]

Development of novel oligonucleotides targeting erythrocyte type B markers for drug delivery applications

نویسندگان [English]

  • K Rahimizadeh 1
  • Gh. Hashemitabar 1
  • M Basami 2
  • A Haghparast 1
  • M Sankian 3
  • R. N. Veedu 4
1 Department of Pathobiology, Faculty of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad, Iran
2 Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad, Iran
3 Immunobiochemistry laboratory, Immunology Research Center, Bu-Ali Research Institute, Mashhad, Iran
4 Center for Comparative Genomics, Murdoch University, Perth 6150, Australia
چکیده [English]

Nucleic acid aptamers have been emerged as potential molecules for target-specific drug delivery because of their ability to bind targets with very high affinity and specificity. Rapid renal clearance is one of the major issues associated with the vascular delivery of nucleic acid-based drugs. To circumvent this problem, this study was designed to envision the development of nucleic acid aptamers specific to human erythrocyte as erythrocytes travel through the cardiovascular system. Erythrocytes have special properties which make them peculiar and specific as a physiological carrier for drug delivery For this purpose, we have performed Cell-SELEX procedure using human erythrocytes containing 4-O-((2-O-(β-D-fucopyranosyl)-3-O-(α-D-galactopyranosyl))-β-galactopyranosyl)-2-acetamido-2-deoxy-α-D-glucopyranoside on the surface as a model target. After completing 15 rounds of selection, sequencing of the product identified RNV543 and RNV544 as potential oligonucleotides specific to the target human erythrocyte. The binding affinity of both RNV543 and RNV544 was confirmed by flowcytometry. This study showed there is Aptamers which can have specific binding to erythrocyte type B.

کلیدواژه‌ها [English]

  • Functional nucleic acids
  • Cell-SELEX
  • oligonucleotides
  • erythrocyte
  • drug deliver

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سابقه مقاله

  • تاریخ دریافت: 07 تیر 1399
  • تاریخ بازنگری: 31 تیر 1399
  • تاریخ پذیرش: 14 مرداد 1399

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