8 documents found, page 1 of 1
Hydrogel-Assisted Antisense LNA Gapmer Delivery for In Situ Gene Silencing in S...
Moreno, PM; Ferreira, AR; Salvador, D; Rodrigues, MT; Torrado, M; Carvalho, ED; Tedebark, U; Sousa, MM; Amaral, IF; Wengel, J; Pêgo, APAfter spinal cord injury (SCI), nerve regeneration is severely hampered due to the establishment of a highly inhibitory microenvironment at the injury site, through the contribution of multiple factors. The potential of antisense oligonucleotides (AONs) to modify gene expression at different levels, allowing the regulation of cell survival and cell function, together with the availability of chemically modified...
Biodegradable PEG-dendritic block copolymers: Synthesis and biofunctionality as...
Leiro, V; Garcia, JP; Moreno, PM; Spencer, AP; Fernandez-Villamarin, M; Riguera, R; Fernandez-Megia, E; Pêgo, APOne important drawback of most of the currently used dendrimers for biomedical applications is their high stability under physiological conditions that can result in cytotoxicity or complications induced by the accumulation of non-degradable synthetic materials in the organism. Particularly in the gene therapy field, vector stability can further hinder the intracellular release of the nucleic acid from the dend...
A high-throughput bioimaging study to assess the impact of chitosan-based nanop...
Gomes, C; Varela-Moreira, A; Leiro, V; Lopes, C; Moreno, PM; Gomez-Lazaro, M; Pêgo, APBy using imaging flow cytometry as a powerful statistical high-throughput technique we investigated the impact of degradation on the biological performance of trimethyl chitosan (TMC)-based nanoparticles (NPs). In order to achieve high transfection efficiencies, a precise balance between NP stability and degradation must occur. We altered the biodegradation rate of the TMC NPs by varying the degree of acetylati...
Delivery of Splice Switching Oligonucleotides by Amphiphilic Chitosan-Based Nan...
Moreno, PM; Santos, J; Gomes, C; Varela-Moreira, A; Costa, A; Leiro, V; Mansur, H; Pêgo, APSplice switching oligonucleotides (SSOs) are a class of single-stranded antisense oligonucleotides (ssONs) being used as gene therapeutics and demonstrating great therapeutic potential. The availability of biodegradable and biocompatible delivery vectors that could improve delivery efficiencies, reduce dosage, and, in parallel, reduce toxicity concerns could be advantageous for clinical translation. In this wor...
Antisense Oligonucleotides Modulating Activation of a Nonsense-Mediated RNA Dec...
Kralovicova, J; Moreno, PM; Cross, N; Pêgo, AP; Vorechovsky, IATM (ataxia-telangiectasia, mutated) is an important cancer susceptibility gene that encodes a key apical kin ase in the DNA damage response pathway. ATM mutations in the germ line result in ataxia-telangiectasia (A-T), a rare genetic syndrome associated with hypersensitivity to double-strand DNA breaks and predisposition to lymphoid malignancies. ATM expression is limited by a tightly regulated nonsense-mediat...
Functionalized chitosan derivatives as nonviral vectors: Physicochemical proper...
Santos, J; Moreno, PM; Mansur, A; Leiro, V; Mansur, H; Pêgo, APCationic polymers have recently attracted attention due to their proven potential for nonviral gene delivery. In this study, we report novel biocompatible nanocomplexes produced using chemically functionalized N,N,N-trimethyl chitosan (TMC) with different N-acyl chain lengths (C 5 -C 18 ) associated with single-stranded oligonucleotides. The TMC derivatives were synthesized by covalent coupling reactions of qua...
Translating chitosan to clinical delivery of nucleic acid-based drugs
Gomes, CP; Lopes, CD; Moreno, PM; Varela-Moreira, A; Alonso, MJ; Pêgo, APA number of systems based on synthetic molecules, among them cationic liposomes and poly(ethylene imine)-based polymers, have been proposed as delivery vehicles for nucleic acids. Some of these systems have even reached the market, ensuring efficient and transient transfection levels in a variety of cell types. However, toxicity issues have limited their application in vivo. In this context, chitosan, a biocomp...
Therapeutic antisense oligonucleotides against cancer: Hurdling to the clinic
Moreno, PM; Pêgo, APUnder clinical development since the early 90's and with two successfully approved drugs (Fomivirsen and Mipomersen), oligonucleotide-based therapeutics has not yet delivered a clinical drug to the market in the cancer field. Whilst many pre-clinical data has been generated, a lack of understanding still exists on how to efficiently tackle all the different challenges presented for cancer targeting in a clinica...