Current progress and limitations of AAV mediated delivery of protein therapeutic genes and the importance of developing quantitative pharmacokinetic/pharmacodynamic (PK/PD) models.
Adv Drug Deliv Rev
; 170: 214-237, 2021 03.
Article
em En
| MEDLINE
| ID: mdl-33486008
ABSTRACT
While protein therapeutics are one of the most successful class of drug molecules, they are expensive and not suited for treating chronic disorders that require long-term dosing. Adeno-associated virus (AAV) mediated in vivo gene therapy represents a viable alternative, which can deliver the genes of protein therapeutics to produce long-term expression of proteins in target tissues. Ongoing clinical trials and recent regulatory approvals demonstrate great interest in these therapeutics, however, there is a lack of understanding regarding their cellular disposition, whole-body disposition, dose-exposure relationship, exposure-response relationship, and how product quality and immunogenicity affects these important properties. In addition, there is a lack of quantitative studies to support the development of pharmacokinetic-pharmacodynamic models, which can support the discovery, development, and clinical translation of this delivery system. In this review, we have provided a state-of-the-art overview of current progress and limitations related to AAV mediated delivery of protein therapeutic genes, along with our perspective on the steps that need to be taken to improve clinical translation of this therapeutic modality.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Terapia Genética
/
Proteínas
/
Dependovirus
Limite:
Humans
Idioma:
En
Revista:
Adv Drug Deliv Rev
Assunto da revista:
FARMACOLOGIA
/
TERAPIA POR MEDICAMENTOS
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Estados Unidos