Nonviral Delivery Systems of mRNA Vaccines for Cancer Gene Therapy

Wang, Yusi; Zhang, Rui; Tang, Lin; Yang, Li

doi:10.3390/pharmaceutics14030512

Cited by 30 publications

(23 citation statements)

References 196 publications

(199 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The COVID-19 pandemic saw a rapid expansion of mRNA-based therapy in medicine with the successful development of a delivery system to produce the COVID-19 mRNA vaccine. A similar delivery system is being explored to deliver siRNA and even aptamers to target biomarkers such as ER or oncogenes in oncogenesis and tumor progression [95].…”

Section: Discussionmentioning

confidence: 99%

The race to develop oral SERDs and other novel estrogen receptor inhibitors: recent clinical trial results and impact on treatment options

Wang

Tang

2022

Cancer Metastasis Rev

View full text Add to dashboard Cite

Hormonal therapy plays a vital part in the treatment of estrogen receptor–positive (ER +) breast cancer. ER can be activated in a ligand-dependent and independent manner. Currently available ER-targeting agents include selective estrogen receptor modulators (SERMs), selective estrogen receptor degraders (SERDs), and aromatase inhibitors (AIs). Estrogen receptor mutation (ESR1 mutation) is one of the common mechanisms by which breast cancer becomes resistant to additional therapies from SERMs or AIs. These tumors remain sensitive to SERDs such as fulvestrant. Fulvestrant is limited in clinical utilization by its intramuscular formulation and once-monthly injection in large volumes. Oral SERDs are being rapidly developed to replace fulvestrant with the potential of higher efficacy and lower toxicities. Elacestrant is the first oral SERD that went through a randomized phase III trial showing increased efficacy, especially in tumors bearing ESR1 mutation, and good tolerability. Two other oral SERDs recently failed to achieve the primary endpoints of longer progression-free survival (PFS). They targeted tumors previously treated with several lines of prior therapies untested for ESR1 mutation. Initial clinical trial data demonstrated that tumors without the ESR1 mutation are less likely to benefit from the SERDs and may still respond to SERMs or AIs, including tumors previously exposed to hormonal therapy. Testing for ESR1 mutation in ongoing clinical trials and in hormonal therapy for breast cancer is highly recommended. Novel protein degradation technologies such as proteolysis-targeting chimera (PROTACS), molecular glue degrader (MGD), and lysosome-targeting chimeras (LYTACS) may result in more efficient ER degradation, while ribonuclease-targeting chimeras (RIBOTAC) and small interfering RNA (siRNA) may inhibit the production of ER protein.

show abstract

Section: Discussionmentioning

confidence: 99%

The race to develop oral SERDs and other novel estrogen receptor inhibitors: recent clinical trial results and impact on treatment options

Wang

Tang

2022

Cancer Metastasis Rev

View full text Add to dashboard Cite

show abstract

“…However, it is di cult to deliver the therapeutic siRNA into the targeted cancer cells and tissues without the assistance of appropriate carriers [12,13]. Generally, the delivery of siRNA for gene therapy was implemented with viral and non-viral carriers [14,15]. Although viral carriers are effective in achieving gene silencing, the risk of insertional mutagenesis and safety concerns over the immunogenicity of the viral vectors have limited their further clinical application [16].…”

Section: Introductionmentioning

confidence: 99%

Engineering siRNA-loaded and RGDfC-targeted selenium nanoparticles for highly efficient silencing of DCBLD2 gene for colorectal cancer treatment

Huang

Chen

Shou

et al. 2023

Preprint

View full text Add to dashboard Cite

Effective and safe delivery of small interfering RNA (siRNA) by nanomaterials to cancer cells is one of the main challenges in cancer treatment. In this study, we constructed the selenium nanoparticles conjugated with RGDfC (one tumor-targeted polypeptide) to prepare a biocompatible gene vector (RGDfC-SeNPs) and then loaded with siDCBLD2 to synthesize the RGDfC-Se@siDCBLD2 for colorectal cancer (CRC) therapy. As expected, RGDfC-SeNPs could enhance the cellular uptake of siDCBLD2 in human HCT-116 colon cancer cells by targeting polypeptide RGDfC on the surface of colon cancer cells. RGDfC-Se@siDCBLD2 could be effectively internalized by HCT-116 cells mainly through a clathrin-related endocytosis pathway. In addition, RGDfC-Se@siDCBLD2 exhibited high siRNA release efficiency in an acidic tumor environment. Moreover, RGDfC-Se@siDCBLD2 could inhibit the proliferation and induce apoptosis in HCT-116 cells by special silencing gene DCBLD2 expression. RGDfC-Se@siDCBLD2 could be specifically accumulated to the tumor sites and exhibited significantly anti-CRC efficacy on HCT-116 tumor-bearing mice without obvious side effects. Taken together, these results suggest that selenium nanoparticles can be used as an effective gene vector with good biocompatibility, and RGDfC-Se@siDCBLD2 provides a promising strategy for combining tumor-target and siRNA delivery in treating CRC.

show abstract

“…[2] They offer fast and flexible approaches for therapeutic functions. [3,4] One of the main limitations of mRNAbased HCC therapy is the need to increase the delivering precision of mRNA molecules in vivo. [5,6] Advancing this property would help distinguish HCC cells from other tissues or in the regulating of cell apoptosis.…”

Section: Introductionmentioning

confidence: 99%

ALPPL2‐Binding Peptide Facilitates Targeted mRNA Delivery for Efficient Hepatocellular Carcinoma Gene Therapy

Lei

Chen

Ming

et al. 2022

Adv Funct Materials

View full text Add to dashboard Cite

mRNA-based gene therapy has emerged as an advanced strategy for hepatocellular carcinoma (HCC) treatment. However, one of its main limitations is lacking delivery precision in vivo. Distinguishing HCC cells from other tissues is crucial for maintaining the high stability, positive therapeutic outcomes, and safety of mRNA therapeutics. Here, a novel HCC specific peptide HCC167 is developed by phage display. It is shown that the HCC167 peptide can specifically recognize variety of HCC substrates including patient samples with high affinity. Modifying nanoparticles with the HCC167 peptide facilitates an effective HCC active targeting ability. When loading with Bims-encoding mRNA, the systemically administrated DMP-HCC167/Bims complex efficiently suppresses HCC progression in multiple models including patient-derived xenografts. Furthermore, the ALPPL2 protein is identified as a specific binding receptor of the HCC167 peptide on the HCC cell membrane, uncovering a new active targeting mechanism based on the HCC167-ALPPL2 ligand-receptor complex. The binding structure is also investigated by computer-aided modeling. The study hence exhibits a potent active targeting strategy for mRNA-based HCC therapy.

show abstract

Nonviral Delivery Systems of mRNA Vaccines for Cancer Gene Therapy

Cited by 30 publications

References 196 publications

The race to develop oral SERDs and other novel estrogen receptor inhibitors: recent clinical trial results and impact on treatment options

The race to develop oral SERDs and other novel estrogen receptor inhibitors: recent clinical trial results and impact on treatment options

Engineering siRNA-loaded and RGDfC-targeted selenium nanoparticles for highly efficient silencing of DCBLD2 gene for colorectal cancer treatment

ALPPL2‐Binding Peptide Facilitates Targeted mRNA Delivery for Efficient Hepatocellular Carcinoma Gene Therapy

Contact Info

Product

Resources

About