Table 1.

Summary of published therapeutic applications of RNA trans-splicing

Target	Disease	Year	5′ or 3′ design	Delivery method	In vitro/in vivo	Reference
AFP	HCC or HPV-16	2018	5′, 3′	transfection	in vitro	Poddar et al.23
Apolipoprotein A1	hemophilia A	2009	3′	injected minicircle	in vivo	Wang et al.24
β-globin	sickle cell disease, β-thalassemia	2017	5′	transfection, lentivirus	in vitro	Uchida et al.25; Kierlin-Duncan et al.26
		2007	5′	transfection	in vitro
β hCG6	cancer	1999	3′	transfection, electroporation	in vitro, in vivo	Puttaraju et al.8
CD22	pediatric B lineage ALL	2015	3′	transfection of polypeptide nanoparticles	in vitro, in vivo	Uckun et al.27,28
		2015	3′	transfection	in vitro
CD40L	X-linked immunodeficiency with HIGM1	2004	3′	transfection, lentivirus	in vitro, in vivo	Tahara et al.29
CEP290	LCA10	2018	5′	AAV	in vitro, in vivo	Dooley et al.30
COL17A1	EB	2011	IER	transfection	in vitro	Koller et al.31; Dallinger et al.32
		2003	3′	transfection	in vitro
COL7A1	EB	2023	3′	minicircle in liposome	in vitro	Koller et al.33; Liemberger et al.34; Mayr et al.35; Peking et al.36,37; Huttner et al.38; Tockner et al.39; Murauer et al.40,41
		2022	5′	retrovirus	in vitro
		2017	3′	lentivirus	in vitro, ex vivo
		2016	IER	retrovirus	in vitro
		2016	3′	retrovirus	in vitro
		2016	5′	transfection, minicircle gene gun	in vitro, in vivo
		2015	3′	transfection	In vitro
		2013	3′	retrovirus	In vitro
		2011	3′	retrovirus	In vitro
Ct-OATP1B3	cancer	2018	3′	transfection, retrovirus	in vitro, in vivo	Sun et al.42
CFTR	cystic fibrosis	2009	segmental	transfection, AAV	in vitro	Liu et al.43; Mansfield et al.44,45; Song et al.46; Liu et al.47
		2005	3′	AAV	in vitro
		2003	5′	transfection	in vitro
		2002	3′	recombinant adenovirus	in vitro, in vivo
		2000	3′	transfection	in vitro
DNA-PKcs	SCID	2007	3′	nucleofection	in vitro	Zayed et al.48
DMPK	DM1	2009	3′	transfection	in vitro	Chen et al.49
DNM2	Autosomal dominant centronuclear myopathy	2016	5′, 3′	transfection, AAV	in vitro, in vivo	Trochet et al.50
DYSF	Dysferlinopathies	2015	3′	lentivirus, AAV	in vitro, in vivo	Philippi et al.51; Monjaret et al.52
		2014	3′	transfection, AAV	in vitro, in vivo
Dystrophin	DMD	2013	3′	transfection, lentivirus, AAV	in vitro, in vivo	Lorain et al.53,54
		2010	IER	transfection	in vitro
FVIII	hemophilia A	2003	3′	transfection, AAV	in vitro, in vivo	Chao et al.55
GNE	GNE myopathy	2014	3′	transfection, AAV	in vitro	Tal-Goldberg et al.56
HIV	HIV	2017	5′, 3′	transfection	in vitro	Ingemarsdotter et al.57
HTT	HD	2017	5′	transfection, lentivirus	in vitro	Rindt et al.58,59
		2012	5′	transfection, lentivirus	in vitro
IgG		2015	segmental	transfection	in vitro	Shang et al.60
KRT14	EB simplex	2019	5′	retrovirus	ex vivo	Liemberger et al.34; Peking et al.61; Wally et al.62
		2018	5′	transfection	in vitro
		2010	5′	transfection	in vitro
LMNA	L-CMD	2018	5′	transfection, AAV	in vitro, in vivo	Azibani et al.63
MAPT	Tauopathies	2018	3′	lentivirus	in vivo	Avale et al.64; Espindola et al.65; Lacovich et al.66; Rodriguez-Martin et al.67,68
		2017	3′	lentivirus	in vitro
		2013	3′	lentivirus	in vitro, in vivo
		2009	3′	transfection	in vitro
		2005	3′	transfection	in vitro
MMP9	EB-SCC	2011	3′	transfection	in vitro	Gruber e al.69
Mybpc3	HCM	2017	5′, 3′	AAV	in vitro	Prondzynski et al.70; Mearini et al.71
		2013	5′	AAV	in vitro, in vivo
PLEC1	EB simplex with muscular dystrophy	2008	5′	transfection, retrovirus	in vitro	Wally et al.72
p53	cancer	2015	3′	transfection, adenovirus	in vitro, in vivo	He et al.73,74
		2015	3′	transfection, adenovirus	in vitro, in vivo
RET protooncogene		2001	3′	transfection	in vitro	Kikumori et al.75
RHO	autosomal dominant retinitis pigmentosa	2015	3′	transfection, AAV	in vitro, in vivo	Berger et al.76
STX1A1	cancer	2005	segmental	adenovirus	in vitro, in vivo	Nakayama et al.77
SLCO1B3	EB-SCC	2013	3′	transfection, retrovirus	in vitro	Gruber et al.78
SMN	SMA	2011	3′	transfection	in vitro, in vivo	Coady et al.79,80,81; Shababi and Lorson82; Shababi et al.83
		2011	3′	transfection	in vivo
		2010	3′	transfection	in vivo
		2008	3′	transfection	in vitro, in vivo
		2007	3′	transfection, AAV	in vitro
SYN1		2018	3′	transfection, lentivirus, AAV	in vitro, in vivo	Davidsson et al.84
TTN	titinopathies	2014	3′	transfection, AAV	in vitro, in vivo	Monjaret et al.52

AAV, adeno-associated virus; AFP, α-fetoprotein; ALL, acute lymphoblastic leukemia; β hCG6, β-subunit of human chorionic gonadotropin gene 6; CD40L, CD40 ligand; CFTR, cystic fibrosis transmembrane conductance regulator; COL17A1, collagen 17A1; COL7A1, type VII collagen; Ct-OATP1B3, cancer-type organic anion transporting polypeptide 1B3; DM1, dystrophia myotonica type 1; DMD, Duchenne muscular dystrophy; DMPK, dystrophia myotonica protein kinase; DNA-PKcs, DNA protein kinase catalytic subunit; DNM2, dynamin 2; DYSF, dysferlin; EB-SCC, epidermolysis bullosa-associated squamous cell carcinoma; FVIII, factor VIII; HCC, hepatocellular carcinoma; GNE, UDP-N-acetylglucosamine 2-epimerase/N-acetyl-mannosamine kinase; HCM, hypertrophic cardiomyopathy; HD, Huntington disease; HIGM1, hyper-immunoglobulin M1; HPV-16, human papillomavirus type 16; HTT, Huntingtin; IgG, immunoglobulin G; IER, internal exon replacement; KRT14, keratin 14; LCA10, Leber congenital amaurosis type 10; L-CMD, LMNA-related congenital muscular dystrophy; LMNA, lamin; MAPT, microtubule-associated protein; MMP9, matrix metalloproteinase-9; PLEC1, plectin; RHO, rhodopsin; SCID, severe combined immune deficiency; SMA, spinal muscular atrophy; SMN, survival motor neuron; STX1A1, shigatoxin1A1; SYN1, synapsin 1; TTN, titin.