• Bridge RNA Technology: A Novel Strategy for Gene Editing in Cancer Treatment
  • Amirsoheil Karami,1 Cobra Moradian,2,*
    1. Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
    2. Department of Medical Biotechnology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran


  • Introduction: Gene editing represents a transformative advancement in contemporary medicine, with CRISPR-Cas9 positioned as the leading technology, facilitating precise modifications within the genome. Still, the restrictions of CRISPR, particularly its hurdles in handling complicated genomic changes tied to conditions like cancer, have driven the pursuit of alternative techniques. One such emergent technique is Bridge RNA (bRNA) editing, which offers a more sophisticated framework for genomic modification. This manuscript examines the underlying mechanisms, potential applications, and initial findings associated with bRNA technology, emphasizing its prospective utility in oncological interventions.
  • Methods: Bridge RNA technology introduces an innovative paradigm of gene editing that transcends the limitations inherent in traditional methodologies such as CRISPR. This technology employs insertion sequence (IS) elements, which are mobile genetic components prevalent in prokaryotic genomes, to facilitate the linkage of disparate DNA sequences. This extraordinary proficiency grants the potential for intricate DNA adjustments, comprising inversions, insertions, and deletions, which are significant for impactful genome engineering. The technology is underpinned by a recombinase protein that operates in conjunction with a guide RNA. This guide RNA delineates two specific sequences: the target locus within the genome necessitating modification and the donor DNA intended to effectuate the alteration. The recombinase is guided by a noncoding bridge RNA (bRNA), which imparts the requisite specificity for accurate DNA recombination. The IS110 family, recognized for encoding this recombinase alongside its corresponding bRNA, is instrumental in facilitating these intricate genomic modifications.
  • Results: Preliminary investigations conducted within bacterial systems have demonstrated that Bridge RNA technology is capable of executing precise and complex genomic alterations. The technology's proficiency in targeting and modifying extensive DNA segments has been corroborated through cryo-electron microscopy analyses, which illustrate the high specificity with which bRNA directs the recombinase to carry out the requisite recombination events. These investigations underscore the versatility of Bridge RNA technology in effectuating diverse forms of genetic modifications—whether it entails the addition, removal, or inversion of DNA sequences. This versatility is particularly salient in the context of cancer treatment, where such extensive genomic rearrangements frequently underpin disease progression. However, notwithstanding the encouraging nature of these preliminary findings, additional research remains imperative to assess the applicability of this technology within human cellular contexts and its potential for clinical implementation.
  • Conclusion: Bridge RNA technology presents a promising new trajectory in gene editing, encompassing significant ramifications for oncological therapy. Its capacity to execute intricate and precise genomic modifications renders it a formidable instrument in addressing the complex genetic alterations characteristic of cancer. Although still in its formative stages and primarily assessed within bacterial systems, the initial results indicate that Bridge RNA may ultimately be developed into a formidable therapeutic alternative. Ongoing research will be crucial to fully actualize its potential within human medicine, potentially ushering in more effective and personalized cancer therapies in the future.
  • Keywords: Bridge RNA, Cancer, Gene Editing