Pre-clinical and clinical importance of miR-21 in human cancers: Tumorigenesis, therapy response, delivery approaches and targeting agents.

The field of non-coding RNA (ncRNA) has made significant progress in understanding the pathogenesis of diseases and has broadened our knowledge towards their targeting, especially in cancer therapy. ncRNAs are a large family of RNAs with microRNAs (miRNAs) being one kind of endogenous RNA which lack encoded proteins. By now, miRNAs have been well-coined in pathogenesis and development of cancer. The current review focuses on the role of miR-21 in cancers and its association with tumor progression. miR-21 has both oncogenic and onco-suppressor functions and most of the experiments are in agreement with the tumor-promoting function of this miRNA. miR-21 primarily decreases PTEN expression to induce PI3K/Akt signaling in cancer progression. Overexpression of miR-21 inhibits apoptosis and is vital for inducing pro-survival autophagy. miR-21 is vital for metabolic reprogramming and can induce glycolysis to enhance tumor progression. miR-21 stimulates EMT mechanisms and increases expression of MMP-2 and MMP-9 thereby elevating tumor metastasis. miR-21 is a target of anti-cancer agents such as curcumin and curcumol and its down-regulation impairs tumor progression. Upregulation of miR-21 results in cancer resistance to chemotherapy and radiotherapy. Increasing evidence has revealed the role of miR-21 as a biomarker as it is present in both the serum and exosomes making them beneficial biomarkers for non-invasive diagnosis of cancer.

Lipid nanoparticles: The game-changer in CRISPR-Cas9 genome editing.

The steady progress in genome editing, especially genome editing based on the use of clustered regularly interspaced short palindromic repeats (CRISPR) and programmable nucleases to make precise modifications to genetic material, has provided enormous opportunities to advance biomedical research and promote human health. However, limited transfection efficiency of CRISPR-Cas9 poses a substantial challenge, hindering its wide adoption for genetic modification. Recent advancements in nanoparticle technology, specifically lipid nanoparticles (LNPs), offer promising opportunities for targeted drug delivery. LNPs are becoming popular as a means of delivering therapeutics, including those based on nucleic acids and mRNA. Notably, certain LNPs, such as Polyethylene glycol-phospholipid-modified cationic lipid nanoparticles and solid lipid nanoparticles, exhibit remarkable potential for efficient CRISPR-Cas9 delivery as a gene editing instrument. This review will introduce the molecular mechanisms and diverse applications of the CRISPR/Cas9 gene editing system, current strategies for delivering CRISPR/Cas9-based tools, the advantage of LNPs for CRISPR-Cas9 delivery, an overview of strategies for overcoming off-target genome editing, and approaches for improving genome targeting and tissue targeting. We will also highlight current developments and recent clinical trials for the delivery of CRISPR/Cas9. Finally, future directions for overcoming the limitations and adaptation of this technology for clinical trials will be discussed.