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The membrane-fusion-based internalization without lysosomal entrapment is advantageous for intracellular delivery over endocytosis. However, protein corona formed on the membrane-fusogenic liposome surface converts its membrane-fusion performance to lysosome-dependent endocytosis, causing poorer delivery efficiency in biological conditions. Herein, we develop an antifouling membrane-fusogenic liposome for effective intracellular delivery in vivo. Leveraging specific lipid composition at an optimized ratio, such antifouling membrane-fusogenic liposome facilitates fusion capacity even in protein-rich conditions, attributed to the copious zwitterionic phosphorylcholine groups for protein-adsorption resistance. Consequently, the antifouling membrane-fusogenic liposome demonstrates robust membranefusion-mediated delivery in the medium with up to 38% fetal bovine serum, outclassing two traditional membrane-fusogenic liposomes effective at 4% and 6% concentrations. When injected into mice, antifouling membrane-fusogenic liposomes can keep their membrane-fusion-transportation behaviors, thereby achieving efficient luciferase transfection and enhancing gene-editingmediated viral inhibition. This study provides a promising tool for effective intracellular delivery under complex physiological environments, enlightening future nanomedicine design. [ABSTRACT FROM AUTHOR]

The emerging field of liquid biopsy has garnered significant interest in precision diagnostics, offering a non-invasive and repetitive method for analyzing bodily fluids to procure real-time diagnostic data. The precision and accuracy offered by the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein (CRISPR/Cas) technology have advanced and broadened the applications of liquid biopsy. Significantly, when combined with swiftly advancing nanotechnology, CRISPR/Cas-mediated nanodevices show vast potential in precise liquid biopsy applications. However, persistent challenges are still associated with off-target effects, and the current platforms also constrain the performance of the assays. In this review, we highlight the merits of CRISPR/Cas systems in liquid biopsy, tracing the development of CRISPR/Cas systems and their current applications in disease diagnosis particularly in liquid biopsies. We also outline ongoing efforts to design nanoscale devices with improved sensing and readout capabilities, aiming to enhance the performance of CRISPR/Cas detectors in liquid biopsy. Finally, we identify the critical obstacles hindering the widespread adoption of CRISPR/Cas liquid biopsy and explore potential solutions. This feature article presents a comprehensive overview of CRISPR/Cas-mediated liquid biopsies, emphasizing the progress in integrating nanodevices to improve specificity and sensitivity. It also sheds light on future research directions in employing nanodevices for CRISPR/Cas-based liquid biopsies in the realm of precision medicine. [ABSTRACT FROM AUTHOR]

Genes are implicated in the manifestation of not only physical traits but also behaviours, moods and mental illnesses. Genetic modification enables the alteration of an individual's characteristics. In addition, some diseases have a genetic origin that can be treated using this method. Genetic engineering is classified into four principal categories: somatic gene therapy, somatic genetic enhancement, germline gene therapy, and germline genetic enhancement. The genetic alterations achieved through somatic gene therapy are confined to the individual undergoing the procedure and are not inherited by subsequent generations. In contrast, the consequences of germline gene therapy persist across multiple generations. The ethical and legal challenges associated with human genetic modification are manifold, with informed consent being a particularly salient issue, particularly in the context of genetic modification of germ cells. Genes are implicated in the manifestation of not only physical traits but also behaviours, moods and mental illnesses. Genetic modification enables the alteration of an individual's characteristics. In addition, some diseases have a genetic origin that can be treated using this method. In this study, we employed an analytical-descriptive methodology to examine this challenge and the perspectives that have been put forth in relation to it. Modern natural law posits reason as the foundation for legal and moral norms, leading to the term "rationalism." The objective of modern natural law or rationalism is to safeguard individual rights. The individual is regarded as the ultimate end, and the principles of individual freedom and the sovereignty of the will are considered to be of paramount importance. This perspective emphasises the importance of undertaking rational tasks in a manner that is guided by benevolent intentions, and posits that the realisation of perfection is contingent upon this approach. The physical and mental faculties serve as the instruments and preliminary steps in the accomplishment of these tasks. From the perspective of rationalism and Kant's thought, people have a moral obligation to pursue their own perfection and that of others. One proposed method for fulfilling this obligation is through genetic modification. However, several principles have been proposed in this thought which are considered to be the most important rational reasons for opposing human genetic modification. Genes are implicated in the manifestation of not only physical traits but also behaviours, moods and mental illnesses. Genetic modification enables the alteration of an individual's characteristics. In addition, some diseases have a genetic origin that can be treated using this method. In this study, we employed an analytical-descriptive methodology to examine this challenge and the perspectives that have been put forth in relation to it. The ethical and legal challenges associated with human genetic modification are particularly pertinent in the context of informed consent, particularly in relation to genetic modifications on germ cells. The question thus arises as to whether an individual is entitled to make a decision to undergo genetic modification with a view to influencing the traits and characteristics of subsequent generations and thereby determining their future and life prospects in a positive or negative manner. This raises the question of whether the principle of informed consent presents an obstacle to human genetic modification. Alternatively, can it be accepted by reference to other rational principles of Kant's moral philosophy, including deontology and the concept of the human being as an end in themselves? What are the human duty and role in perfecting themselves and others on this basis? Is proxy consent accepted by Kant's rational view and can it replace the consent of the patient or a person who is created in the future or not? Given that the majority of objections to human genetic modification have a Kantian basis, is such an approach correct and complete? If this view is not correct, can a view in favour of genetic modification be inferred from Kant's thought? The initial stage of the discussion centred on an examination of the fundamental principles, concepts and categories of informed consent. This was followed by an investigation into the constituent elements of the process of informed consent and the circumstances under which the principle of informed consent can be applied. In addition, the potential implications of this principle for the field of genetic modification were considered. Finally, this study analyses the effect of Kantian dutyism and the concept of the human being as an end in itself on genetic modification. It seems that genetic modification does not necessarily mean violating the rights of individuals, and on the other hand, embryos or even germ cells do not have free will, which can be seen as an obstacle to genetic modification. Moreover, human beings have a duty to the happiness of others, and parents have a duty to their children. Although this duty is in conflict with the duty to respect individual autonomy and informed consent, the way out of the conflict is to emphasise the results orientation and to pay attention to the end of the human being, because there is no basis for preferring one of these two tasks over the other, and therefore Kant's thought is blocked in this respect. In this way, the treatment of diseases of genetic origin and the provision of a better life through the development of the individual's traits is the cause and introduction to other rational tasks, in other words, the positive results of genetic modification are preferable to the obstacle of lack of conscious consent. Acceptance of genetic modification and exit will result from this blockage and conflict, and therefore the duty to fulfil the duties of the parents is superior to the duty to respect the individual autonomy of the foetus, and in the meantime there is a difference in the therapeutic goal or the strengthening goal in germline methods or somatic in children will not be incompetent. Finally, according to Kant's view of duty, genetic modification of human embryos can be accepted. [ABSTRACT FROM AUTHOR]

It has recently been argued that reproductive genetic manipulation technologies like mitochondrial replacement and germline CRISPR modifications cannot be said to save anyone's life because, counterfactually, no one would suffer more or die sooner absent the intervention. The present article argues that, on the contrary, reproductive genetic manipulations may be life-saving (and, from this, have therapeutic value) under an appropriate population health perspective. As such, popular reports of reproductive genetic manipulations potentially saving lives or preventing disease are not necessarily mistaken, though such terminology still requires further empirical validation. [ABSTRACT FROM AUTHOR]