University of Bonn, Medical School, Venusberg-Campus 1, Bonn, Germany.
Eur Rev Med Pharmacol Sci. 2024 Mar;28(6):2430-2463. doi: 10.26355/eurrev_202403_35751.
Human Immunodeficiency Virus (HIV) has continuously been the greatest epidemic for humanity over a period spanning almost five decades. With no specific cure or treatment available to date despite extensive research, the C-C Chemokine Receptor 5, Delta 32 (CCR5 Δ32) allele genetic point mutation plays an imperative role in the prevention of acquired immunodeficiency syndrome (AIDS). This comprehensive study aims to review the induction of the homozygous recessive deletion genotype using the Clustered Regularly Interspaced Short Palindromic Repeats, Cas 9 Enzyme (CRISPR-Cas9), and hematopoietic stem cell transplantation under positive selection pressure for active immunity in seropositive patients' populations as the phenotype. A methodology is proposed to trigger a significant increase in the expression of Delta 32 beneficial mutant alleles within controlled modern healthcare facilities utilizing totipotent stem cells through somatic gene therapy. It acts upon two dysfunctional CCR5 genes, translating mutant G protein-coupled co-receptors, whose primary function is similar to that of C-X-C Motif Chemokine receptor 4 (CXCR4), by blocking the entry of viral RNA into the CD4+ T helper lymphocytes, halting infection and seizing viral life cycle. This modification is endemic in Northern Europe, where it naturally pertains to the Caucasian descent population samples in the form of polymorphism, p (X=0.01), where X is the probability of frequency of complete immunity against HIV-1 in population samples. The epigenetics of the single nucleotide polymorphism (SNP) are analyzed as they play a significant role in immunity distribution. Furthermore, a comparative analysis within the ethical boundaries of CRISPR-Cas9 is conducted to discuss the practical aspects and challenges of the presented methodologies and treatment alternatives. Additionally, the study assembles all available data and summarizes preexisting research while providing a promising solution to this ethical dilemma. Finally, a methodology is devised to answer the question of whether the variant-specific epidemic of AIDS caused by HIV-1 can be cured via artificially inducing immunity by CRISPR-Cas9.
人类免疫缺陷病毒 (HIV) 在过去近五十年的时间里一直是人类最大的流行病。尽管进行了广泛的研究，但迄今为止仍然没有特定的治愈方法或治疗方法，C-C 趋化因子受体 5、Delta 32（CCR5 Δ32）等位基因遗传点突变在预防获得性免疫缺陷综合征 (AIDS) 方面发挥了至关重要的作用。本综合研究旨在综述使用簇状规则间隔短回文重复序列、Cas9 酶 (CRISPR-Cas9) 诱导纯合隐性缺失基因型，并在阳性选择压力下对血清阳性患者群体中的造血干细胞移植进行主动免疫，作为表型。提出了一种方法，通过体细胞基因治疗，利用多能干细胞在受控的现代医疗保健设施中触发 Delta 32 有益突变等位基因的显著表达增加。它作用于两个功能失调的 CCR5 基因，翻译突变的 G 蛋白偶联共受体，其主要功能类似于 C-X-C 基序趋化因子受体 4 (CXCR4)，通过阻止病毒 RNA 进入 CD4+T 辅助淋巴细胞，阻止感染并抓住病毒生命周期。这种修饰在北欧地区很普遍，在那里它以多态性的形式自然存在于北欧血统人群样本中，p（X=0.01），其中 X 是人群样本中对 HIV-1 完全免疫的概率频率。单核苷酸多态性 (SNP) 的表观遗传学被分析，因为它们在免疫分布中起着重要作用。此外，在 CRISPR-Cas9 的伦理界限内进行了比较分析，讨论了所提出的方法和治疗选择的实际方面和挑战。此外，该研究还收集了所有可用数据并总结了现有研究，为这一伦理困境提供了一个有希望的解决方案。最后，设计了一种方法来回答通过 CRISPR-Cas9 人工诱导免疫是否可以治愈由 HIV-1 引起的艾滋病变体特异性流行的问题。
