Over the past decade, CRISPR has rapidly made its way from the bench to the bedside, providing a newfound therapeutic avenue to not only treat genetic diseases but also permanently cure them. Although there are several clinical trials in early stages, there are so far no CRISPR-based clinical trials for cutaneous disease. In this review, we describe multiple cutaneous diseases that represent ideal targets for CRISPR-based therapeutics owing to known single gene‒causing mutations. We also explore the potential of CRISPR nucleases to treat inflammatory disorders such as eczema and psoriasis, which are not classically categorized as genodermatoses. We describe the therapeutic solutions for these diseases that are guided by various CRISPR-associated (Cas) effector proteins, for example, using Cas9 to permanently edit the DNA of somatic cells, Cas3 to target foreign DNA to combat viral/bacterial skin infections, and Cas13 to edit mutated RNA transcripts in diseases where permanent DNA editing is untenable. Furthermore, we discuss various drug delivery modalities for CRISPR therapeutics, including transdermal patches and microneedles, which are uniquely suited for dermatological diseases. In summary, we highlight the potential of CRISPR-based therapeutics to revolutionize the treatment of cutaneous disease with a goal of being accessible to the practicing dermatologist.

T cells are critical to fight pathogenic microbes and combat malignantly transformed cells in the fight against cancer. To exert their effector function, T cells produce effector molecules, such as the pro-inflammatory cytokines IFN-γ, TNF-α and IL-2. Tumors possess many inhibitory mechanisms that dampen T cell effector function, limiting the secretion of cytotoxic molecules. As a result, the control and elimination of tumors is impaired. Through recent advances in genomic editing, T cells can now be successfully modified via CRISPR/Cas9 technology. For instance, engaging (post-)transcriptional mechanisms to enhance T cell cytokine production, the retargeting of T cell antigen specificity or rendering T cells refractive to inhibitory receptor signaling can augment T cell effector function. Therefore, CRISPR/Cas9-mediated genome editing might provide novel strategies for cancer immunotherapy. Recently, the first-in-patient clinical trial was successfully performed with CRISPR/Cas9-modified human T cell therapy. In this review, a brief overview of currently available techniques is provided, and recent advances in T cell genomic engineering for the enhancement of T cell effector function for therapeutic purposes are discussed.

Upon pathogen invasion, bacteria and archaea activate an RNA-interference-like mechanism termed CRISPR (clustered regularly interspaced short palindromic repeats). A large family of Cas (CRISPR-associated) proteins mediates the different stages of this sophisticated immune response. Bioinformatic studies have classified the Cas proteins into families, according to their sequences and respective functions. These range from the insertion of the foreign genetic elements into the host genome to the activation of the interference machinery as well as target degradation upon attack. Cas7 family proteins are central to the type I and type III interference machineries as they constitute the backbone of the large interference complexes. Here we report the crystal structure of Thermofilum pendens Csc2, a Cas7 family protein of type I-D. We found that Csc2 forms a core RRM-like domain, flanked by three peripheral insertion domains: a lid domain, a Zinc-binding domain and a helical domain. Comparison with other Cas7 family proteins reveals a set of similar structural features both in the core and in the peripheral domains, despite the absence of significant sequence similarity. T. pendens Csc2 binds single-stranded RNA in vitro in a sequence-independent manner. Using a crosslinking - mass-spectrometry approach, we mapped the RNA-binding surface to a positively charged surface patch on T. pendens Csc2. Thus our analysis of the key structural and functional features of T. pendens Csc2 highlights recurring themes and evolutionary relationships in type I and type III Cas proteins.