Recent Advancements in Reducing the Off-Target Effect of CRISPR-Cas9 Genome Editing.

The CRISPR-Cas (Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)) and the associated protein (Cas9) system, a young but well-studied genome-editing tool, holds plausible solutions to a wide range of genetic disorders. The single-guide RNA (sgRNA) with a 20-base user-defined spacer sequence and the Cas9 endonuclease form the core of the CRISPR-Cas9 system. This sgRNA can direct the Cas9 nuclease to any genomic region that includes a protospacer adjacent motif (PAM) just downstream and matches the spacer sequence. The current challenge in the clinical applications of CRISPR-Cas9 genome-editing technology is the potential off-target effects that can cause DNA cleavage at the incorrect sites. Off-target genome editing confuses and diminishes the therapeutic potential of CRISPR-Cas9 in addition to potentially casting doubt on scientific findings regarding the activities of genes. In this review, we summarize the recent technological advancements in reducing the off-target effect of CRISPR-Cas9 genome editing.

Current updates on generations, approvals, and clinical trials of CAR T-cell therapy.

Chimeric antigen receptor (CAR) T-cell therapy is a novel, customized immunotherapy that is considered a 'living' and self-replicating drug to treat cancer, sometimes resulting in a complete cure. CAR T-cells are manufactured through genetic engineering of T-cells by equipping them with CARs to detect and target antigen-expressing cancer cells. CAR is designed to have an ectodomain extracellularly, a transmembrane domain spanning the cell membrane, and an endodomain intracellularly. Since its first discovery, the CAR structure has evolved greatly, from the first generation to the fifth generation, to offer new therapeutic alternatives for cancer patients. This treatment has achieved long-term and curative therapeutic efficacy in multiple blood malignancies that nowadays profoundly change the treatment landscape of lymphoma, leukemia, and multiple myeloma. But CART-cell therapy is associated with several hurdles, such as limited therapeutic efficacy, little effect on solid tumors, adverse effects, expensive cost, and feasibility issues, hindering its broader implications.

Ciltacabtagene autoleucel: The second anti-BCMA CAR T-cell therapeutic armamentarium of relapsed or refractory multiple myeloma.

Ciltacabtagene autoleucel (also known as cilta-cel) is a chimeric antigen receptor (CAR) T-cell therapy that targets B-cell maturation antigen (BCMA) on the surface of cancer cells in B cell malignancies, such as multiple myeloma (MM). It is a second-generation CAR that is outfitted with an ectodomain comprising two BCMA-binding single chain variable fragment (ScFv) domains, a transmembrane domain, and an endodomain possessing CD3ζ and 4-1BB. Cilta-cel is an autologous, gene-edited CAR T-cell that is prepared by collecting and modifying the recipient's T-cells to create a patient personalized treatment in the laboratory to be infused back. This CAR T-cell product exceptionally entails CARs with two BCMA-targeting single-domain antibodies that detect two epitopes of BCMA expressed on the malignant cells of MM. Cilta-cel is the current addition to the treatment armamentarium of relapsed or refractory (r/r) MM after its approval by the FDA on February 28, 2022, based on the results of the Phase 1b/2 CARTITUDE-1 study. It was the second approved anti-BCMA CAR T-cell product after idecabtagene vicleucel (ide-cel) to treat myeloma patients. It induces early, deep, and long-lasting responses with a tolerable safety profile in r/r MM. Cilta-cel-treated myeloma patients may potentially experience adverse effects ranging from mild to life-threatening, but they are mostly manageable toxicities. Besides, it has a consistent safety profile upon a longer follow-up of patients. Cilta-cel generally outperforms ide cel in terms of efficacy in MM, but shows comparable adverse events. This review highlights the current updates on cilta-cel efficacy, adverse events, comparison with ide-cel, and its future direction in the treatment of MM.

Mutational Pattern, Impacts and Potential Preventive Strategies of Omicron SARS-CoV-2 Variant Infection.

Since the emergence of COVID 19, the authentic SARS-CoV-2 has evolved into a range of novel variants that are of more global concern. In late November 2021, the Omicron (lineage B.1.1.529) variant was identified as a new variant and considered as the fifth variant of concern. Omicron harbors a genetic profile that is exceedingly unusual, with a huge number of mutations. Above thirty mutations are localized in the S protein, while some are found in other structural and non-structural proteins. Half of the mutations in the S protein are in the RBD, which is a major target of antibodies, showing that Omicron mutations may affect antibody binding affinity to the S protein. The Omicron variant has been found to result in immune escape, therapeutic or vaccine escape, as well as increased transmissibility and reinfection risk, explaining its rapid international spread that sparks a global alarm even more serious than the previously reported variants. Omicron has the capability to bypass at least some of the multi-faceted immune responses induced by prior infection or vaccination. It is shown to extensively escape neutralizing antibodies while evading cell mediated immune defense to a lesser extent. The efficacy of COVID 19 vaccines against Omicron variant is decreased with primary vaccination, showing that the vaccine is less efficient in preventing Omicron infections. However, after receiving a booster vaccine dose, the immunological response to Omicron significantly improved and hold promising results. Despite the mild nature of the disease in most vaccinated people, the rapid spread of Omicron, as well as the increased risk of re-infection, poses yet another major public health concern. Therefore, effort should be devoted to maintaining the existing COVID 19 preventive measures as well as developing new vaccination strategies in order to control the fast dissemination of Omicron.

Knowledge and Proportion of COVID-19 Vaccination and Associated Factors Among Cancer Patients Attending Public Hospitals of Addis Ababa, Ethiopia, 2021: A Multicenter Study.

BACKGROUND: Cancer patients are classified as being at high risk of contracting COVID-19 infection, hospitalization, and death and were recommended to have early access to the limited COVID-19 vaccine. However, there are limited studies on the knowledge and acceptance of the COVID-19 vaccine among cancer patients. Therefore, this study aimed at assessing the awareness, readiness, and associated factors among cancer patients. METHODS: Institution-based cross-sectional study was conducted on 422 cancer patients from May to August, 2021. A structured interviewer-administered questionnaire was used to collect primary data. A systematic random sampling technique was used to select study participants. Descriptive statistics and binary logistic regression followed by multivariable analysis were performed to investigate the independent association of factors with the outcome variable. Finally, statistical significance was declared at P <0.05 using AOR and 95% CI. RESULTS: From the 422 cancer patients who participated, 77 (18.2%) had a history of COVID-19 infection, and 224 (55%) believe that the cancer disease will not make them more vulnerable to be infected by COVID-19. Accordingly, younger age (18-30 years) (AOR = 2.73: 95% CI: 0.18, 4.51), female (AOR = 6.4: 95% CI: 0.7, 13.8), having information about COVID-19 vaccine (AOR = 6.9: 95% CI: 3.1, 15.2), COVID-19 infection history (AOR = 6.0: 95% CI: 2.5, 11.8), duration since cancer diagnosis (≥10 years) (AOR= 6.2: 95% CI: 2.6, 14.7), and belief about the likelihood of dying of COVID-19 infection (AOR = 3.05: 95% CI: 1.03, 4.05) were the independent predictors of the likelihood of receiving COVID-19 vaccine among cancer patients. CONCLUSION: This study has found significant cancer patients with poor knowledge about the vaccine, and the percentage of both the first and second round of COVID-19 vaccination was small. Therefore, information communication with cancer patients and oncologists about the COVID-19 vaccine may help to decrease vaccine hesitancy.

Knowledge and attitude of the community towards epilepsy in Northwest Ethiopia: A huge gap on knowledge and attitude of the community.

BACKGROUND: Misconception about epilepsy in Ethiopia is higher which in turn affects overall quality of life of the individuals. This research was aimed to assess knowledge and attitude of the community towards epilepsy in Northwest Ethiopia. METHODS: A community-based cross-sectional study was conducted. Data was entered by Epi data version 4.2 and analyzed by SPSS version 24. Descriptive and analytical statistical procedures, with 95% confidence interval were employed and significance level was determined at p-value < 0.05. RESULT: A total of 782 respondents were participated with the response rate of 96.1%. About 66.2% of respondents had poor knowledge and 67.0% had unfavorable attitude, towards epilepsy.In multivariate logistic regression, younger age, rural resident, not knew someone with epilepsy, did not have witness of seizure episode, and did not take prior training were associated with poor knowledge. Male sex, rural resident, did not know someone with epilepsy, did not have witness of seizure episode, did not take prior training, and had poor knowledge were associated with unfavorable attitude towards epilepsy. CONCLUSION: Majority of participants had poor knowledge and unfavorable attitude. Public education about epilepsy is recommended to modify misconceptions and to promote positive attitudes.