OMEGA endonuclease
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OMEGA (obligate mobile element guided activity) systems are a class of RNA-guided DNA targeting systems encoded by transposable elements.[1] They include an OMEGA endonuclease (TnpB, IscB or IsrB) which cleaves DNA, and a non-coding guide RNA, called ωRNA, which guides the enzyme to a target sequence.[1][2] Like Cas enzymes, to cleave DNA, OMEGA endonucleases must first recognize a specific DNA sequence, called a transposon-adjacent motif (TAM, akin to a protospacer-adjacent motif).[3] OMEGA systems occur in both prokaryotes and eukaryotes.[1][4][5]
History
[edit]Originally reported and named in 2021 by a team centered around the labs of Feng Zhang and Eugene Koonin, OMEGA systems were identified as likely evolutionary precursors to the CRISPS-Cas systems, namely the endonucleases Cas9 and Cas12.[3] The original paper, published in Science, reported on both the IscB and TnpB endonucleases,[3] and a subsequent 2021 paper (from the lab of Virginijus Šikšnys, published in Nature) reported on the TnpB endonuclease.[4]
In 2023, the Fanzor endonuclease was discovered in eukaryotic cells, and is generally considered an OMEGA endonuclease.[1][5]
The primary significance of the discovery of each of these systems is considered to be their potential for use in gene editing.[1][3][4][5]
Application in gene editing
[edit]Much of the application to date using OMEGA systems has been early and comparative. For example, early work showed that the indel patterns of these systems closely mimic that of Cas12a.[1] To date, no OMEGA system has been applied in human disease.[2][6]
OMEGA systems are compact in size in comparison to most CRISPR-Cas systems (excluding Cas12). Thus, unlike Cas9 systems, they are able to be packaged in an adeno-associated virus (AAV) vector, allowing delivery into living human tissues for therapeutic purposes.[1][6] Sickle cell disease is considered to be a good candidate for applications of OMEGA systems, including Fanzor.[6]
References
[edit]- 1 2 3 4 5 6 7 Badon, Isabel Wen; Oh, Yeounsun; Kim, Ho-Joong; Lee, Seung Hwan (2024-01-03). "Recent application of CRISPR-Cas12 and OMEGA system for genome editing". Molecular Therapy: The Journal of the American Society of Gene Therapy. 32 (1): 32–43. doi:10.1016/j.ymthe.2023.11.013. ISSN 1525-0024. PMC 10787141. PMID 37952084.
- 1 2 Chang, Chin-Wei; Truong, Vy Anh; Pham, Nam Ngoc; Hu, Yu-Chen (2024). "RNA-guided genome engineering: paradigm shift towards transposons". Trends in Biotechnology. 42 (8): 970–985. doi:10.1016/j.tibtech.2024.02.006. ISSN 1879-3096. PMID 38443218.
- 1 2 3 4 Altae-Tran, Han; Kannan, Soumya; Demircioglu, F. Esra; Oshiro, Rachel; Nety, Suchita P.; McKay, Luke J.; Dlakić, Mensur; Inskeep, William P.; Makarova, Kira S.; Macrae, Rhiannon K.; Koonin, Eugene V.; Zhang, Feng (2021). "The widespread IS200/IS605 transposon family encodes diverse programmable RNA-guided endonucleases". Science. 374 (6563): 57–65. Bibcode:2021Sci...374...57A. doi:10.1126/science.abj6856. ISSN 1095-9203. PMC 8929163. PMID 34591643.
- 1 2 3 Karvelis, Tautvydas; Druteika, Gytis; Bigelyte, Greta; Budre, Karolina; Zedaveinyte, Rimante; Silanskas, Arunas; Kazlauskas, Darius; Venclovas, Česlovas; Siksnys, Virginijus (2021). "Transposon-associated TnpB is a programmable RNA-guided DNA endonuclease". Nature. 599 (7886): 692–696. Bibcode:2021Natur.599..692K. doi:10.1038/s41586-021-04058-1. ISSN 1476-4687. PMC 8612924. PMID 34619744.
- 1 2 3 Saito, Makoto; Xu, Peiyu; Faure, Guilhem; Maguire, Samantha; Kannan, Soumya; Altae-Tran, Han; Vo, Sam; Desimone, AnAn; Macrae, Rhiannon K.; Zhang, Feng (2023). "Fanzor is a eukaryotic programmable RNA-guided endonuclease". Nature. 620 (7974): 660–668. Bibcode:2023Natur.620..660S. doi:10.1038/s41586-023-06356-2. ISSN 1476-4687. PMC 10432273. PMID 37380027.
- 1 2 3 Alhumoudi, Aisha Yousef; Alotaibi, Aminah Ghazi; Alosaimi, Nada Fahad; Alshalani, Abdulrahman; Alqahtani, Saad M.; Alsaab, Sarah M.; Almutiri, Basem Jahz; Albariqi, Mohammed M. H. (2026). "CRISPR and Fanzor in sickle cell disease: current progress and future prospects". Frontiers in Genome Editing. 8 1774014. doi:10.3389/fgeed.2026.1774014. ISSN 2673-3439. PMC 13246667. PMID 42273255.