Table 5.
Other targets.
| References | Objectives | Study design | Disease models | Delivery methods | Targets | Effects |
|---|---|---|---|---|---|---|
| Ruan et al. (73) | Evaluate functionality of HDV-PRG4 in OA mouse model | Preclinical in vivo | Mouse ACLT model | HDV-PRG4 | PRG4 | Improved histology scores, cartilage volume and coverage |
| Ruan et al. (74) | Development of a targeted vector for chondrocyte-specific delivery of target genes for OA therapy | Preclinical in vivo | Mouse ACLT model | (Modified) helper-dependent adenovirus: (a10mab)HDV-PRG4 | PRG4 | Prevention of OA development with early treatment with both HDV-PRG4 and a10mabHDV-PRG4; greater efficacy of a10mabHDV-PRG4; preserved cartilage volume and surface area; with late treatment, greater preservation of cartilage volume; larger bone area covered by cartilage with a10mabHDV-PRG4 compared to HDV-PRG4 vector, resulting in 10-fold reduction of effective dosage requirement for preventing post-ACTL OA |
| Stone et al. (75) | Evaluate the beneficial effects of a combinatorial gene therapy approach compared to monotherapy | Preclinical in vivo | Mouse DMM and mouse ACLT model | Helper-dependent adenovirus: HDV-NFκB-IL1ra and HDV-EF1-PRG4 | IL-1Ra and PRG4 | ACLT model: better preservation of cartilage volume and covered surface area in combined therapy; prevented decrease of anabolic gene expression and upregulation of inflammatory and catabolic pathways; DMM model: maintained cartilage volume and covered surface area of underlying bone in combined and PRG4 therapy; longer prevention of OA-induced thermal hyperalgesia with combined therapy |
| Seol et al. (76) | Evaluate functionality of recombinant PRG4-GFP fusion protein in delaying OA progression | Preclinical in vivo | Rabbit ACLT model | Adenoassociated virus: AAV-PRG4-GFP | PRG4 | Reduced post-ACLT severity of PTOA; higher percentage of cartilage surface and superficial chondrocytes coated with lubricin |
| Tashkandi et al. (77) | Assess the potential of LOXL2 to be used for translational research and clinical applications in OA treatment | Preclinical in vitro | IL-1β stimulated ATDC5 cartilage cell line | Adenovirus: Adv-RFP-LOXL2 | LOXL2 | Blunted decrease of Acan and Sox9; attenuated expression of Adamts4/5 and MMP13; attenuated IL-1β induced NF-κB activity |
| Preclinical in vivo | Chondrodysplasia (Cho/+) mice | Protection against progressive OA: increased proteoglycan deposition; increased expression of aggrecan and Col2; decreased expression of Mmp13 and Adamts5; increased expression of anabolic genes | ||||
| MIA-induced LOXL2 transgenic mice | LOXL2 transgenic mice (loxP-PGK-neo-stop-loxP-LOXL2-IRES-eGFP) | Protection against MIA-induced proteoglycan and aggrecan degradation and decreased Mmp13 expression; protection against MIA-induced OA-related decline in knee function | ||||
| Venkatesan et al. (78) | Develop a non-viral gene transfer strategy to stimulate GAG synthesis to promote cartilage repair | Preclinical in vitro | IL-1β stimulated primary rat chondrocytes; IL-1β stimulated cartilage explants | Transfection of pShuttle-GlcAT-I using PEI | GlcAT-I | Inhibited IL-1β induced loss of PGs; increased GAG content but no influence on chain size; increased amount of CS chains; restored PG synthesis in IL-1β treated cartilage explants |
| Fu et al. (79) | Explore the effect of GGCX overexpression on ACLT-induced OA | Preclinical in vivo | Rabbit ACLT model | Lentivirus GGXC | GGCX | Reduced morphological changes caused by ACLT; increased cMPG to normal levels; decreased ACLT-induced inflammation (expression of TNFα and IL-1β); decreased collagen type X and MMP13 expression, increased collagen type II expression |
| Hsieh et al. (80) | Evaluate the effects of Ad-mediated kallistatin overexpression in OA rat model | Preclinical in vivo | Rat ACLT model | Adenovirus: AdHKBP | Kallistatin | Reduced inflammatory response (IL-1β and TNF-α levels in joints); reduced OA severity and apoptosis; decreased macrophage infiltration; reduced hyperplasia and synovitis |
| Ashraf et al. (81) | Determine effect of Rheb on phenotype and function of OA chondrocytes | Preclinical in vitro | Human articular OA chondrocytes | Transfection of pEGFP-N1 vector using microporator | RHEB | Normalized morphology; reduced senescence; decreased oxidative stress |
| Determine effect of Rheb expression on OA progression in mice | Preclinical in vivo | Mouse DMM model | Adenovirus: Ad-Rheb | Attenuated cartilage destruction; suppressed expression of Adamts5, Mmp13, Col10 and Col2a1; inhibited apoptosis | ||
| Grossin et al. (82) | Determine efficiency of gene transfer with HSP70 in rat patellar cartilage | Preclinical in vivo | Rat MIA model | Transfection of pcDNA3.1/CT-GFP-HSP70 by electroporation | HSP70 | Inhibited endochondral ossification in the deep layer; reduced severity of OA-induced lesions |
| Yoon et al. (83) | Identify the role of PUM1 in OA progression | Preclinical in vivo | Mouse DMM model | Lentivirus: pLenti-GII-CMV-PUM1 | PUM1 | Reduced cartilage destruction; less chondrocyte loss; reduced OARSI score |
| Na et al. (84) | Asses the therapeutic potential of sCCR2 E3 for OA | Preclinical in vivo | Rat MIA model | sCCR2 E3 vector via electroporation | sCCR2 E3 | Reduced pain; less bone loss and cartilage degradation; lower OARSI and Mankin score; inhibition of IL-1β, IL-6 and MMP-13 expression |
| Cao et al. (85) | Elucidate the role of cholesterol-LRP3 axis in OA | Preclinical in vitro | TNFa-induced rat OA chondrocytes | Lentivirus: Lv-Lrp3 | LRP3 | Increased expression of anabolic genes COL2A1, ACAN, SOX9; increased proteoglycan and GAG |
| Preclinical in vivo | Rat ACLT model | Less cartilage degradation; rescued proteoglycan and type II collagen level; milder OA phenotype; increased expression of anabolic genes COL2A1, ACAN, SOX9; decreased expression of catabolic genes Adamts5 and Mmp13 |