Overall, the story of HIV is one of astounding success. But to declare victory, it will be necessary to develop a vaccine. The opening session of the 31st Conference on Retroviruses and Opportunistic Infections (CROI) 2024 looked back to the failures but also the advances in research, all the steps that over the years brought the basic science knowledge that could bring an HIV vaccine in the future. This year, the former director of the Viral Pathogenesis Laboratory at the NIAID Vaccine Research Center, Barney Graham, was named for the Bernard Field Lecture, where he presented “Modern vaccinology: a legacy of HIV research.”

An Italian group of researchers has used zinc finger editing to silence the PCSK9 gene and improve blood cholesterol levels in mice by applying a single dose of their modifier. The epigenetic-based method could be an alternative to genome editing.

Bruton tyrosine kinase (BTK) enzyme inhibitors used to treat B-cell cancers, including chronic lymphocytic leukemia and non-Hodgkin lymphoma, also produce resistance by causing mutations in the protein. Now, a study on the BTK degrader NX-2127 showed the compound could be effective in eliminating BTK regardless of its mutations.

Using interactions between viral peptides and human proteins as a starting point, researchers from Enyo Pharma Inc., the University of Lyon and other institutions were able to bootstrap themselves to a mitochondria-targeting small molecule that showed activity in a mouse model of nonalcoholic steatohepatitis (NASH) with chronic kidney disease.

The field of peptides is exploding, Perpetual Medicines Corp. co-founder, chairman and CEO Kerry L. Blanchard recently told BioWorld, “with a projected growth rate far surpassing large and small molecules, and gene therapies. The area is underinvested, too, so this is a good opportunity to focus on peptide therapeutics.”

If we unraveled the DNA of the 46 chromosomes of a single human cell, it would barely measure 2 meters. If we did the same with the rest of the body, if we aligned the 3 billion base pairs of its 5 trillion cells, we could travel the distance from the Earth to the Sun more than 100 times. It seems unreachable. However, that is the unit of knowledge of the large sequencing projects achieved in 2023. From the generation of the human pangenome to cell-by-cell maps of the brain and kidneys, scientists this year have completed several omics collaborative projects stored in large international databases. Now, what’s the plan?

Modifying a patient’s DNA is no longer just for science fiction novels. The CRISPR gene editing technique developed by Jennifer Doudna and Emmanuelle Charpentier only took 10 years to reach the market as Casgevy (exagamglogene autotemcel/exa-cel, Vertex Pharmaceuticals Inc.), treating congenital pathologies such as β-thalassemia and severe sickle cell disease. But science does not stop.

Artificial Intelligence (AI) driven tools have the ability to design new drugs, with a bit of help from humans, said Anders Hogner, from Astrazeneca plc’s R&D department at the Bio-IT World Conference & Expo Europe in London. “We don’t have anything out there yet,” he added, but the company appears to be working on it.

Investigators at the Chinese Academy of Sciences have generated a chimeric monkey by injecting an embryonic stem cell into the morula, which is an extremely early embryo consisting of 16 to 32 cells. The animal survived for only 10 days, and it is not the first live birth of a chimeric primate. But it is the first such chimera with contributions from an embryonic stem cell, and that stem cell contributed a far higher proportion of cells in the newborn than have been achieved in previous attempts at creating chimeras.

At the 30th Annual Congress of the European Society for Gene and Cell Therapy in Brussels this week, researchers presented both preclinical and clinical strategies for applying gene therapy to a functional HIV cure. At a Wednesday session on Infectious Diseases & Vaccines, Alessio Nahmad, of Tabby Therapeutics Ltd., described using B cells edited to express broadly neutralizing antibodies (bnAbs) 3BNC117 to deliver high titers of antibodies in mice.