Genasense (oblimersen)

(+)-JQ1-Oblimersen showed increased effectiveness in an acute myeloid leukemia cell model, showing that this therapeutic may merit re-evaluation. This work demonstrates that the covalent modification of ASOs with a small-molecule nuclear importer can significantly improve target engagement and pave the way for more effective therapeutics.

To overcome the drawback of poor water solubility of PDT, HA/G3139/Ce6@Fe3O4 nanosystem was synthesized, which combines the benefits of G3139 antisense oligonucleotides for gene therapy and hyaluronic acid for encapsulation and targeting CD44 receptor...The novel nanosystem demonstrates synergistic anti-cancer effects by combining PDT, gene therapy, and chemodynamic therapy, leading to enhanced apoptosis in breast cancer cells. In conclusion, this approach offers a promising strategy for more effective and targeted breast cancer treatment.

So far, pre-clinical and clinical studies showed promising results when Bcl-2 (Genasense), Mcl-1 (ISIS2048), STAT3 (ISIS345794) and IRF4 (ION251) were targeted using ASOs-based formulations. The relevant genetic targets in ASOs-based MM therapies were described, and the research results obtained in the studies conducted so far were analyzed, with a focus on the ASOs formulations that were already included in clinical trials. In the end, current challenges, and future perspectives of antisense therapy for MM were also discussed.

Meanwhile, the released functional nucleic acid G3139 downregulated the expression of Bcl-2, and accelerated the apoptosis of tumor cells. In conclusion, the HTCG@TA demonstrated significant effect in oxidative damage amplification and tumor inhibition both in vitro and in vivo, which has provided a new outlook for the clinical application of chemo-dynamic tumor treatment and synergistic gene therapy with self-delivery nanoplatforms.

Our team designed a new Antisense Oligonucleotide (ASO) based on Antisense oligo G3139. It also had a synergistic effect with the Tamoxifen. The cationic nano-complex (Niosome) was more efficient than the liposome in delivering designed oligo antisense Bcl-2 in the cancer cells.

P1, N=37, Terminated, University of Nebraska | Phase classification: P=N/A --> P1

In this study, a chemotherapy drug-free nanotherapeutic system based on ZIF-90 encapsulated with Ce6-G3139 and Ce6-DNAzyme for gene and photodynamic therapies was constructed...In addition, the photosensitizer Ce6 carried by the nucleic acid will produce cytotoxic ROS to kill cancer cells after irradiation. The results of this study demonstrated that the designed nanoplatform, which synergistically combines gene and photodynamic therapies, has shown great potential for cancer treatment.

Throughout the years, many Bcl-2 family inhibitors have been developed, with Venetoclax being now successfully used in treating hematological malignancies...We managed to include clinical trials of various phases which analyze the pharmacokinetics and pharmacodynamics of the drugs, as well as the effectiveness and adverse effects. Active and recruiting clinical trials are also briefly presented and future prospects and challenges are discussed.

The results illustrate that aCD33-NKSN/G3139 nanoparticles could improve the antitumor activity of encapsulated G3139 due to aCD33 targeting and the ability to perform nuclear localization, The results offer a promising clinical application potential for the treatment of acute myeloid leukemia. A R T I C L E I N F O.

In a phase 1 study of AML patients treated with G3139, cytarabine, and daunorubicin induction with cytarabine consolidation, no antisense-related toxicity was reported, and BCL2 downregulation occurred in patients achieving complete remission. However, more effective means of inhibiting BCL2 are showing promising results in combination with chemotherapy in AML. This trial was registered at www.clinicaltrials.gov as #NCT00085124.