ZFIN ID: ZDB-PUB-160915-6
Internal Oligoguanidinium-based Cellular Transporter Enhances Antisense Efficacy of Morpholinos in in vitro and Zebrafish model
Bhadra, J., Pattanayak, S., Khan, P.P., Kundu, J., Sinha, S.
Date: 2016
Source: Bioconjugate Chemistry   27(10): 2254-2259 (Journal)
Registered Authors: Pattanayak, Sankha, Sinha, Surajit
Keywords: none
MeSH Terms:
  • Animals
  • Boron Compounds/chemistry
  • CHO Cells
  • Cell Line
  • Circular Dichroism
  • Cricetulus
  • Embryo, Nonmammalian
  • Fetal Proteins/genetics
  • Fetal Proteins/metabolism
  • Mice
  • Microscopy, Atomic Force
  • Morpholinos
  • NIH 3T3 Cells
  • Oligonucleotides, Antisense/administration & dosage*
  • Oligonucleotides, Antisense/chemistry*
  • Oligonucleotides, Antisense/pharmacokinetics
  • T-Box Domain Proteins/genetics
  • T-Box Domain Proteins/metabolism
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Zinc Finger Protein GLI1/genetics
PubMed: 27625020 Full text @ Bioconjug. Chem.
Efficient cellular transporter is highly desirable for the therapeutic applications of antisense phosphorodiamidate morpholino oligonucleotides (PMOs) as Vivo-PMO and PPMO have limitations for in-vivo study. We report here a novel internally tetraguanidinium linked nonpeptidic cellular transporter having conformationally rigid backbone composed of pharmacologically compatible heterocyclic six-membered rings which internalizes efficiently into cells in full growth medium and ubiquitously distributed into zebrafish embryos. It efficiently transports antisense PMO in-vitro and in-vivo zebrafish embryos. Comparative study with Gene Tools Vivo-PMO revealed that our cellular-transporter conjugated PMO shows better antisense efficacy.