TABLE 1

Examples of emerging techniques to deliver therapy in patients with COPD and idiopathic pulmonary fibrosis (IPF) and their limitations

Technique	Description	Uses and advances made with the technique	Current limitations
PROTAC	Proteolysis-targeting chimaera that uses the cell's ubiquitin–proteasome system to target-specific proteins for degradation	Could induce the degradation of proteins previously considered “undruggable” [50] Highly selective for the target protein, with rapid, effective and prolonged degradation of the target [51] Valuable for mechanisms requiring precise targeting for degradation	Can only target a protein for degradation, not for modification
CRISPR	Can manipulate gene function through gene deletion, correction or replacement; enhancement of gene expression; base editing	Huge potential for target-specific genetic medication for gene therapy in COPD and IPF to target dysregulated genes or pathways (e.g. epigenetic changes to genes implicated in mucus hypersecretion in COPD) [52]	Concerns exist around safety and off-target effects; these are under investigation [53]
Inhaled antisense oligonucleotides	Single-stranded DNA or RNA (20–21 base pairs) complementary to the target mRNA	Knocks down the expression of the target gene [54] Can modulate molecules that cannot be targeted using antibodies [54] Inhalation could minimise toxicities associated with systemic exposure of antisense oligonucleotides [54]	Currently in the investigational stage Intracellular delivery to the site of action is a challenge [54]
Exosomes as delivery systems	A potential delivery system for nucleic acid drugs	Potential use in delivering drugs such as antagomirs or miRNA molecules, thanks to their low antigenicity and toxicity [55] Could target particular cell types In vitro and in vivo studies have shown promise in successfully delivering molecules [56]	Currently in the investigational stage

PROTAC: proteolysis-targeting chimaera; CRISPR: clustered regularly interspaced short palindromic repeats.