Progress in Respiratory Gene Therapy.
Hum Gene Ther
; 33(17-18): 893-912, 2022 09.
Article
in English
| MEDLINE | ID: covidwho-2271618
ABSTRACT
The prospect of gene therapy for inherited and acquired respiratory disease has energized the research community since the 1980s, with cystic fibrosis, as a monogenic disorder, driving early efforts to develop effective strategies. The fact that there are still no approved gene therapy products for the lung, despite many early phase clinical trials, illustrates the scale of the challenge In the 1990s, first-generation non-viral and viral vector systems demonstrated proof-of-concept but low efficacy. Since then, there has been steady progress toward improved vectors with the capacity to overcome at least some of the formidable barriers presented by the lung. In addition, the inclusion of features such as codon optimization and promoters providing long-term expression have improved the expression characteristics of therapeutic transgenes. Early approaches were based on gene addition, where a new DNA copy of a gene is introduced to complement a genetic mutation however, the advent of RNA-based products that can directly express a therapeutic protein or manipulate gene expression, together with the expanding range of tools for gene editing, has stimulated the development of alternative approaches. This review discusses the range of vector systems being evaluated for lung delivery; the variety of cargoes they deliver, including DNA, antisense oligonucleotides, messenger RNA (mRNA), small interfering RNA (siRNA), and peptide nucleic acids; and exemplifies progress in selected respiratory disease indications.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Peptide Nucleic Acids
Type of study:
Experimental Studies
/
Prognostic study
Language:
English
Journal:
Hum Gene Ther
Journal subject:
Genetics, Medical
/
Therapeutics
Year:
2022
Document Type:
Article
Affiliation country:
Hum.2022.172
Similar
MEDLINE
...
LILACS
LIS