A Comprehensive Review of Non-Surgical Treatments for Hypertrophic and Keloid Scars in Skin of Color.

Hypertrophic and keloid scars are fibroproliferative growths resulting from aberrant wound healing. Individuals with Fitzpatrick skin types (FSTs) IV-VI are particularly predisposed to hypertrophic and keloid scarring, yet specific guidelines for these populations are still lacking within the literature. Therefore, this comprehensive review provides a list of various treatments and considerations for hypertrophic and keloid scarring in patients with skin of color. We constructed a comprehensive PubMed search term and performed quadruple-blinded screening on all resulting studies to achieve this objective. Our findings demonstrate 1) the lack of efficacious treatments for raised scars within this population and 2) the need to empirically investigate individualized and multimodal therapeutic options for those with skin of color.

Beyond the Surface: A Deeper Look at the Psychosocial Impacts of Acne Scarring.

Post-acne scarring is a common consequence of acne vulgaris with no universal cure. Although there have been many recent advances to address acne scars physically, there is still a lack of research that investigates their psychosocial impacts. Our comprehensive PubMed search presents an overview of existing information to highlight known sources of mental distress caused by post-acne scarring, both related to and independent of the psychosocial detriments caused early on by active acne. The literature indicates that acne scarring is a distinct condition from acne vulgaris and therefore requires a comprehensive clinical approach unique from those available for active acne.

Subcision for Atrophic Acne Scarring: A Comprehensive Review of Surgical Instruments and Combinatorial Treatments.

Subcutaneous incisionless surgery, also known as subcision, is a minimally invasive procedure that is commonly indicated for the treatment of atrophic acne scars. In recent years, many new techniques have been developed to maximize results from this procedure. This review article aims to identify an updated list of instruments and combinatorial treatments available for atrophic acne scar patients undergoing subcision. We constructed a comprehensive PubMed search term and performed triple-blinded screening on all resulting studies for mentions of subcision as indicated by acne scarring. Our results show that there are four main categories of subcision tools that are commonly employed to treat atrophic acne scars: needles, cannulas, wires, and blunt-blade instruments. Usage of these devices varies by scar depth, personal preference, and combinatorial treatment options. Overall, subcision is a particularly effective treatment for atrophic acne scars, and there is vast potential for further innovation with this technique.

A Comprehensive Review of Non-Energy-Based Treatments for Atrophic Acne Scarring.

Scarring is a dire consequence of acne vulgaris. Particularly, atrophic acne scarring is highly prevalent among young adults, and its physical and psychological effects can persist throughout their lives if left untreated. This literature review will analyze various non-energy-based approaches to treating atrophic acne scarring, emphasizing recent advances within the last 5 to 10 years. To accomplish this, we performed a PubMed search for various acne scar treatments such as chemical peels, dermabrasion, microdermabrasion, subcision, microneedling, punch techniques, dermal fillers, and thread lifting. Our findings and analysis show that there is no panacean solution to treating atrophic acne scars, which explains the evolving trend towards developing unique combinatorial treatments. Although a fair comparison of each treatment approach is difficult to achieve due to the studies' varying sample sizes, strength of evidence, treatment execution, etc, there still remains a level of consensus on what treatments are well suited for particular scar types.

Improved lentiviral vector titers from a multi-gene knockout packaging line.

Lentiviral vectors (LVs) are robust delivery vehicles for gene therapy as they can efficiently integrate transgenes into host cell genomes. However, LVs with lengthy or complex expression cassettes typically are produced at low titers and have reduced gene transfer capacity, creating barriers for clinical and commercial applications. Modifications of the packaging cell line and methods may be able to produce complex vectors at higher titer and infectivity and may improve production of many different LVs. In this study, we identified two host restriction factors in HEK293T packaging cells that impeded LV production, 2'-5'-oligoadenylate synthetase 1 (OAS1) and low-density lipoprotein receptor (LDLR). Knocking out these two genes separately led to ∼2-fold increases in viral titer. We created a monoclonal cell line, CRISPRed HEK293T to Disrupt Antiviral Response (CHEDAR), by successively knocking out OAS1, LDLR, and PKR, a previously identified factor impeding LV titers. Packaging in CHEDAR yielded ∼7-fold increases in physical particles, full-length vector RNA, and vector titers. In addition, overexpressing transcription elongation factors, SPT4 and SPT5, during packaging improved the production of full-length vector RNA, thereby increasing titers by ∼2-fold. Packaging in CHEDAR with over-expression of SPT4 and SPT5 led to ∼11-fold increases of titers. These approaches improved the production of a variety of LVs, especially vectors with low titers or with internal promoters in the reverse orientation, and may be beneficial for multiple gene therapy applications.

ß-Globin Lentiviral Vectors Have Reduced Titers due to Incomplete Vector RNA Genomes and Lowered Virion Production.

Lentiviral vectors (LVs) commonly used for the treatment of hemoglobinopathies often have low titers and sub-optimal gene transfer efficiency for human hematopoietic stem and progenitor cells (HSPCs), hindering clinical translation and commercialization for ex vivo gene therapy. We observed that a high percentage of ß-globin LV viral genomic RNAs were incomplete toward the 3' end in packaging cells and in released vector particles. The incomplete vector genomes impeded reverse transcription in target cells, limiting stable gene transfer to HSPCs. By combining three modifications to vector design and production (shortening the vector length to 5.3 kb; expressing HIV-1 Tat protein during packaging; and packaging in PKR-/- cells) there was a 30-fold increase in vector titer and a 3-fold increase in vector infectivity in HSPCs. These approaches may improve the manufacturing of ß-globin and other complex LVs for enhanced gene delivery and may facilitate clinical applications.

Creating New ß-Globin-Expressing Lentiviral Vectors by High-Resolution Mapping of Locus Control Region Enhancer Sequences.

Hematopoietic stem cell gene therapy is a promising approach for treating disorders of the hematopoietic system. Identifying combinations of cis-regulatory elements that do not impede packaging or transduction efficiency when included in lentiviral vectors has proven challenging. In this study, we deploy LV-MPRA (lentiviral vector-based, massively parallel reporter assay), an approach that simultaneously analyzes thousands of synthetic DNA fragments in parallel to identify sequence-intrinsic and lineage-specific enhancer function at near-base-pair resolution. We demonstrate the power of LV-MPRA in elucidating the boundaries of previously unknown intrinsic enhancer sequences of the human ß-globin locus control region. Our approach facilitated the rapid assembly of novel therapeutic ßAS3-globin lentiviral vectors harboring strong lineage-specific recombinant control elements capable of correcting a mouse model of sickle cell disease. LV-MPRA can be used to map any genomic locus for enhancer activity and facilitates the rapid development of therapeutic vectors for treating disorders of the hematopoietic system or other specific tissues and cell types.

Improved Titer and Gene Transfer by Lentiviral Vectors Using Novel, Small ß-Globin Locus Control Region Elements.

ß-globin lentiviral vectors (ß-LV) have faced challenges in clinical translation for gene therapy of sickle cell disease (SCD) due to low titer and sub-optimal gene transfer to hematopoietic stem and progenitor cells (HSPCs). To overcome the challenge of preserving efficacious expression while increasing vector performance, we used published genomic and epigenomic data available through ENCODE to redefine enhancer element boundaries of the ß-globin locus control region (LCR) to construct novel ENCODE core sequences. These novel LCR elements were used to design a ß-LV of reduced proviral length, termed CoreGA-AS3-FB, produced at higher titers and possessing superior gene transfer to HSPCs when compared to the full-length parental ß-LV at equal MOI. At low vector copy number, vectors containing the ENCODE core sequences were capable of reversing the sickle phenotype in a mouse model of SCD. These studies provide a ß-LV that will be beneficial for gene therapy of SCD by significantly reducing the cost of vector production and extending the vector supply.