Research Article Details
| Article ID: | A29380 |
| PMID: | 34159305 |
| Source: | JHEP Rep |
| Title: | Novel vectors and approaches for gene therapy in liver diseases. |
| Abstract: | Gene therapy is becoming an increasingly valuable tool to treat many genetic diseases with no or limited treatment options. This is the case for hundreds of monogenic metabolic disorders of hepatic origin, for which liver transplantation remains the only cure. Furthermore, the liver contains 10-15% of the body's total blood volume, making it ideal for use as a factory to secrete proteins into the circulation. In recent decades, an expanding toolbox has become available for liver-directed gene delivery. Although viral vectors have long been the preferred approach to target hepatocytes, an increasing number of non-viral vectors are emerging as highly efficient vehicles for the delivery of genetic material. Herein, we review advances in gene delivery vectors targeting the liver and more specifically hepatocytes, covering strategies based on gene addition and gene editing, as well as the exciting results obtained with the use of RNA as a therapeutic molecule. Moreover, we will briefly summarise some of the limitations of current liver-directed gene therapy approaches and potential ways of overcoming them. |
| DOI: | 10.1016/j.jhepr.2021.100300 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| S17 | Genetic therapy | Genetic approaches; genetherapy; Gene therapy | HSD17B13 inhibitor; PNPLA3-rs7 38409 (I148M) variant inhibitor; PNPLA3 expression down-regulator | INI-678; Momelotinib | Details |
| S10 | Liver transplantation | -- | -- | -- | Details |
| S15 | Cell therapy | Mesenchymal stem cells; Stem cell therapy | -- | -- | Details |
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D328 | Serine | Chemical drug | DB00133 | SRR | Improve insulin resistance | Under clinical trials | Details |
| D395 | Zinc | Chemical drug | DB01593 | PSPH; CCS; HDAC1 cofactor; HDAC4 cofactor; INS; UTRN; ASPA cofactor; TP73 cofactor; A2M; AGT; APOBR; APOE; APOL1; C3; C5; CFB; CFH; CFI; CLU; CP; CPN2; DSP; F12; F13B; FGA; GSN; HBB; HPR; JUP; SELENOP; TTR; VTN | -- | Under clinical trials | Details |
| D589 | Minor allele-specific small interfering RNA | Miscellany | -- | PNPLA3-rs738409 (I148M) variant inhibitor | -- | Under investigation | Details |
| D080 | Citrulline | Chemical drug | DB00155 | -- | -- | Under clinical trials | Details |
| D316 | S-adenosyl-L-methionine | Chemical drug | DB00118 | GNMT cofactor | Antiviral | Under clinical trials | Details |