Digging into the lesser-known aspects of CRISPR biology

Guzmán, Noemí M.; Esquerra-Ruvira, Belen; Mojica, Francisco J. M.

doi:10.1007/s10123-021-00208-7

Cited by 11 publications

(6 citation statements)

References 330 publications

(493 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The role of the Cas2 protein has not been identified thus far. However, this protein has RNase and DNase activities and is essential for the adaptation phase in Escherichia coli ( E. coli ) ( Guzmán et al, 2021 ). The most frequently used subtype of CRISPR/Cas systems is the type II CRISPR/Cas9, employed for gene editing in eukaryotic cells ( Table 1 ) ( Makarova et al, 2020 ; Ramachandran et al, 2020 ).…”

Section: Types and Classes Crispr/cas Systemsmentioning

confidence: 99%

Nanocarriers: A novel strategy for the delivery of CRISPR/Cas systems

et al. 2022

View full text Add to dashboard Cite

In recent decades, clustered regularly interspaced short palindromic repeat/CRISPR-associated protein (CRISPR/Cas) has become one of the most promising genome-editing tools for therapeutic purposes in biomedical and medical applications. Although the CRISPR/Cas system has truly revolutionized the era of genome editing, the safe and effective delivery of CRISPR/Cas systems represents a substantial challenge that must be tackled to enable the next generation of genetic therapies. In addition, there are some challenges in the in vivo delivery to the targeted cells/tissues. Nanotechnology-based drug delivery systems can be employed to overcome this issue. This review discusses different types and forms of CRISPR/Cas systems and the current CRISPR/Cas delivery systems, including non-viral carriers such as liposomes, polymeric, and gold particles. The focus then turns to the viral nanocarriers which have been recently used as a nanocarrier for CRISPR/Cas delivery.

show abstract

Section: Types and Classes Crispr/cas Systemsmentioning

confidence: 99%

Nanocarriers: A novel strategy for the delivery of CRISPR/Cas systems

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Transcripts from the CRISPR array are processed into small RNA molecules (crRNA), each containing a fragment of a single spacer and part of the repeats. The following steps of the CRISPR mechanism may show substantial variations depending on the system type 9 . In the type II CRISPR-Cas system, associated with the signature Cas9 effector protein (referred to as the CRISPR-Cas9 system), the crRNA molecules bound to an accessory trans-activating crRNA (tracrRNA), serve as cognate guides (gRNAs) for the Cas9 nuclease.…”

Section: Introductionmentioning

confidence: 99%

Evolution of CRISPR-associated endonucleases as inferred from resurrected proteins

et al. 2023

View full text Add to dashboard Cite

Clustered regularly interspaced short palindromic repeats (CRISPR)-associated Cas9protein is an effector that plays a major role in a prokaryotic adaptive immune system, by which invading DNA can be targeted and cut for inactivation. The Cas9 endonuclease is directed to target sites by a guide RNA (gRNA) where Cas9 can recognize specific sequences (PAMs) in foreign DNA, which then serve as an anchoring point for cleavage of the adjacent RNA-matching DNA region. Although the CRISPR-Cas9 system has been widely studied and repurposed for diverse applications (notably, genome editing), its origin and evolution remain to be elucidated. Here, we investigate the evolution of Cas9 from resurrected ancient nucleases (anCas) in extinct firmicutes species as old as 2600 myr to the current day. Surprisingly, we demonstrate that these ancient forms were much more flexible in their PAM and gRNA scaffold requirements compared to modern day Cas9 enzymes. In addition, anCas portrays a gradual paleoenzymatic adaptation from nickase to double-strand break activity, suggesting a mechanism by which ancient CRISPR systems could propagate when harboring Cas enzymes with minimal PAMs. The oldest anCas also exhibit high levels of activity with ssDNA and ssRNA targets, resembling Cas nucleases in related system types. Finally, we illustrate editing activity of the anCas enzymes in human cells. The prediction and characterization of anCas proteins uncovers an unexpected evolutionary trajectory leading to ancient enzymes with extraordinary properties.

show abstract

“…In addition to influencing bacterial behaviors, CRISPR-Cas systems might also have a role in influencing the immune systems of eukaryotic cells, helping bacteria evade host defense mechanisms. In this article, we will discuss some latest advances in the effects of CRISPR-Cas systems on the physiological and virulence alteration of bacteria and potential mechanisms as well as the impact of CRISPR-Cas-mediated gene regulation on mammalian host response, more detailed coverage of other relevant CRISPR-Cas researches may be found elsewhere [26][27][28].…”

Section: Introductionmentioning

confidence: 99%

CRISPR-Cas systems target endogenous genes to impact bacterial physiology and alter mammalian immune responses

Cui

Liu

et al. 2022

Mol Biomed

View full text Add to dashboard Cite

CRISPR-Cas systems are an immune defense mechanism that is widespread in archaea and bacteria against invasive phages or foreign genetic elements. In the last decade, CRISPR-Cas systems have been a leading gene-editing tool for agriculture (plant engineering), biotechnology, and human health (e.g., diagnosis and treatment of cancers and genetic diseases), benefitted from unprecedented discoveries of basic bacterial research. However, the functional complexity of CRISPR systems is far beyond the original scope of immune defense. CRISPR-Cas systems are implicated in influencing the expression of physiology and virulence genes and subsequently altering the formation of bacterial biofilm, drug resistance, invasive potency as well as bacterial own physiological characteristics. Moreover, increasing evidence supports that bacterial CRISPR-Cas systems might intriguingly influence mammalian immune responses through targeting endogenous genes, especially those relating to virulence; however, unfortunately, their underlying mechanisms are largely unclear. Nevertheless, the interaction between bacterial CRISPR-Cas systems and eukaryotic cells is complex with numerous mysteries that necessitate further investigation efforts. Here, we summarize the non-canonical functions of CRISPR-Cas that potentially impact bacterial physiology, pathogenicity, antimicrobial resistance, and thereby altering the courses of mammalian immune responses.

show abstract

Digging into the lesser-known aspects of CRISPR biology

Cited by 11 publications

References 330 publications

Nanocarriers: A novel strategy for the delivery of CRISPR/Cas systems

Nanocarriers: A novel strategy for the delivery of CRISPR/Cas systems

Evolution of CRISPR-associated endonucleases as inferred from resurrected proteins

CRISPR-Cas systems target endogenous genes to impact bacterial physiology and alter mammalian immune responses

Contact Info

Product

Resources

About