Reactions to the National Academies/Royal Society Report on Heritable Human Genome Editing.

In September 2020, a detailed report on Heritable Human Genome Editing was published. The report offers a translational pathway for the limited approval of germline editing under limited circumstances and assuming various criteria have been met. In this perspective, some three dozen experts from the fields of genome editing, medicine, bioethics, law, and related fields offer their candid reactions to the National Academies/Royal Society report, highlighting areas of support, omissions, disagreements, and priorities moving forward.

Preimplantation diagnosis to create 'saviour siblings': a critical discussion of the current and future legal frameworks in South Africa.

Pre-implantation genetic diagnosis (PGD) is a technology used in conjunction with in vitro fertilisation to screen embryos for genetic conditions prior to transfer. It was initially developed to screen mutations for severe, irreversible, genetic conditions. Currently, PGD makes it possible to select against more than 100 different genetic conditions. It has been proposed as a method for creating a tissue-matched child who can in turn serve as a compatible stem cell donor to save a sick sibling in need of a stem cell transplant. The advantage of this method is that it provides genetic information before implantation of an embryo into the womb, making it possible to ensure that only tissue-matched embryos are transferred to the uterus. A couple can therefore avoid the difficult choice of either terminating the pregnancy at a later point if the fetus is not a match, or extending their family again in the hope that their next child will be tissue compatible. Many people have expressed disapproval of the use of PGD for this purpose, and it is associated with many conflicting interests including religion, ethics as well as legal regulation. In order to manage these issues some jurisdictions have created legal frameworks to regulate the use of this technology. Many of these are modelled on the UK's Human Fertilisation and Embryology Authority and its guardian legislation. This paper critiques the current and future South African legal framework to establish whether it is able to adequately regulate the use of PGD as well as guard against misuse of the technology. It concludes that changes are required to the future framework in order to ensure that it regulates the circumstances in which PGD may occur and that the Minister of Health should act expediently in finalising draft regulations which will regulate PGD in the future.

Polymeric nanoparticle-encapsulated curcumin ("nanocurcumin"): a novel strategy for human cancer therapy.

BACKGROUND: Curcumin, a yellow polyphenol extracted from the rhizome of turmeric (Curcuma longa), has potent anti-cancer properties as demonstrated in a plethora of human cancer cell line and animal carcinogenesis models. Nevertheless, widespread clinical application of this relatively efficacious agent in cancer and other diseases has been limited due to poor aqueous solubility, and consequently, minimal systemic bioavailability. Nanoparticle-based drug delivery approaches have the potential for rendering hydrophobic agents like curcumin dispersible in aqueous media, thus circumventing the pitfalls of poor solubility. RESULTS: We have synthesized polymeric nanoparticle encapsulated formulation of curcumin - nanocurcumin - utilizing the micellar aggregates of cross-linked and random copolymers of N-isopropylacrylamide (NIPAAM), with N-vinyl-2-pyrrolidone (VP) and poly(ethyleneglycol)monoacrylate (PEG-A). Physico-chemical characterization of the polymeric nanoparticles by dynamic laser light scattering and transmission electron microscopy confirms a narrow size distribution in the 50 nm range. Nanocurcumin, unlike free curcumin, is readily dispersed in aqueous media. Nanocurcumin demonstrates comparable in vitro therapeutic efficacy to free curcumin against a panel of human pancreatic cancer cell lines, as assessed by cell viability and clonogenicity assays in soft agar. Further, nanocurcumin's mechanisms of action on pancreatic cancer cells mirror that of free curcumin, including induction of cellular apoptosis, blockade of nuclear factor kappa B (NFkappaB) activation, and downregulation of steady state levels of multiple pro-inflammatory cytokines (IL-6, IL-8, and TNFalpha). CONCLUSION: Nanocurcumin provides an opportunity to expand the clinical repertoire of this efficacious agent by enabling ready aqueous dispersion. Future studies utilizing nanocurcumin are warranted in pre-clinical in vivo models of cancer and other diseases that might benefit from the effects of curcumin.

Delivery of hydrophobised 5-fluorouracil derivative to brain tissue through intravenous route using surface modified nanogels.

Random copolymeric micelles composed of N-isopropylacrylamide (NIPAAM) and N-vinylpyrrolidone (VP) cross-linked with N,N'-methylenebisacrylamide (MBA) have been used as nanogel carriers to encapsulate N-hexylcarbamoyl-5-fluorouracil (HCFU), a prodrug of 5-FU, and have been targeted to brain tissue across blood-brain barrier (BBB) after coating with polysorbate 80. Accumulation of nanogel particles in the brain and other tissues of "strain A" mice had been monitored by radiolabeling of nanogels with (99m)Tc. Gamma Scintigraphic technique was also performed to see the distribution of (99m)Tc labeled nanogels in the brain. The retention time in blood appeared to be slightly longer for coated nanogels than that of uncoated nanogels though the accumulation of coated nanogels in the RES was more or less same as that of uncoated nanogels. The blood however had almost double accumulation of polysorbate 80 coated nanogels in the initial 5 min compared to that shown by uncoated nanogels. We speculate that coating of nanogels with polysorbate 80 alters the surface properties of nanogels, which results in relatively higher uptake in the brain tissue. The studies revealed that a large portion of (99m)Tc labeled HCFU loaded nanogels are accumulated in the RES (lung, liver and spleen). The accumulation of the labeled nanogels in the brain, however, is much less compared to RES and it has been found that while an amount of uncoated labeled nanogels was found to be 0.18% of the injected dose, it increased to 0.52% on coating with polysorbate 80. The optimal amount of polysorbate 80 added to nanogels for the maximum delivery of particles to brain was found to be 1% w/w. These results were further supported by the gamma scintigrams of New Zealand rabbits. Thus, the present nanogel system has opened a new avenue for poorly soluble drugs to be targeted to brain by coating the particles with polysorbate 80.