Peptidic tools applied to redirect alternative splicing events.
Peptides are versatile and attractive biomolecules that can be applied to modulate genetic mechanisms like alternative splicing. In this process, a single transcript yields different mature RNAs leading to the production of protein isoforms with diverse or even antagonistic functions. During splicing events, errors can be caused either by mutations present in the genome or by defects or imbalances in regulatory protein factors. In any case, defects in alternative splicing have been related to several genetic diseases including muscular dystrophy, Alzheimer's disease and cancer from almost every origin. One of the most effective approaches to redirect alternative splicing events has been to attach cell-penetrating peptides to oligonucleotides that can modulate a single splicing event and restore correct gene expression. Here, we summarize how natural existing and bioengineered peptides have been applied over the last few years to regulate alternative splicing and genetic expression. Under different genetic and cellular backgrounds, peptides have been shown to function as potent vehicles for splice correction, and their therapeutic benefits have reached clinical trials and patenting stages, emphasizing the use of regulatory peptides as an exciting therapeutic tool for the treatment of different genetic diseases.
Laboratorio de Ecología Molecular Microbiana, Centro de Investigaciones en Ciencias Microbiológicas, Instituto de Ciencias, Benemérita Universidad Autónoma de Puebla, Mexico.
Martínez-Montiel
MM
Nancy
Laboratorio de Bioquímica y Biología Molecular, Instituto de Ciencias, Benemérita Universidad Autónoma de Puebla, Mexico.
Rosas-Murrieta
RM
Nora
Laboratorio de Ecología Molecular Microbiana, Centro de Investigaciones en Ciencias Microbiológicas, Instituto de Ciencias, Benemérita Universidad Autónoma de Puebla, Mexico. Electronic address: rebeca.martinez@correo.buap.mx.
Martínez-Contreras
MC
Rebeca
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D057846:Cell-Penetrating Peptides / Q000378:metabolism* / Q000494:pharmacology; D030342:Genetic Diseases, Inborn / Q000628:therapy; D006801:Humans; D008969:Molecular Sequence Data; D020135:Peptide Nucleic Acids / Q000378:metabolism* / Q000494:pharmacology; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D014162:Transfection
D057846:Cell-Penetrating Peptides; D020135:Peptide Nucleic Acids; D020033:Protein Isoforms
Cell-penetrating peptide; Mutations; Peptide nucleic acid; Splicing; mRNA