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This Week in Science: Jul 15, 2011

In this week's Science, Harvard University's George Church and his colleagues "present genome engineering technologies that are capable of fundamentally reengineering genomes from the nucleotide to the megabase scale." Called multiplex automated genome engineering and conjugative assembly genome engineering, or MAGE and CAGE, Church et al.'s methods "treat the chromosome as both an editable and an evolvable template, permitting the exploration of vast genetic landscapes," they write. Gerald Joyce, who was not involved in this study, tells The New York Times that "it is a major technical breakthrough which has great promise for scientific breakthroughs to follow." In comparing Church et al.'s work with the genome-engineering achievements of Craig Venter and his team, Joyce says: "Craig builds the house from scratch, and George is more the remodeler, but they are both interesting houses to live in."

Elsewhere in this week's issue, the University of California, Berkeley's Barbara Meyer and her colleagues present what they call a "broadly applicable strategy using zinc finger nucleases and transcription activator-like effector nucleases for targeted disruption of endogenous genes and cis-acting regulatory elements in diverged nematode species." In its discussion, the team suggests its strategy is "broadly useful" as it "brings targeted mutagenesis to non-model organisms and facilitates dissection of diverse biological processes."

In a Science paper published online in advance this week, investigators at Memorial Sloan-Kettering Cancer Center and elsewhere show that a fusion protein, AML1-ETO, "is acetylated by p300 in leukemia cells isolated from t [translocation] (8;21) AML patients and is essential for its self-renewal promoting effects in human cord blood CD34+ cells and its leukemogenicity in mouse models." Because of these observations, the team suggests lysine acetyltransferases as potential therapeutic targets for AML.

Researchers at Rockefeller University and their colleagues report the cloning and characterization of 576 new HIV antibodies from four unrelated individuals, all of whom "produced expanded clones of potent broadly neutralizing CD4-binding site antibodies that mimic binding to CD4," they write. In its molecular genetics analysis, the team found that these new antibodies share "a consensus sequence of 68 immunoglobulin H chain amino acids and arise independently from two related IgH genes." The team also reports significant sequence convergence among a group of agonistic CD4bs antibodies, or HAADs, and says that these "might contribute to viremic control in a subset of HIV-infected individuals, and may be useful in HIV prevention or possibly even therapy because of the low concentrations required for viral neutralization."

The Scan

Self-Reported Hearing Loss in Older Adults Begins Very Early in Life, Study Says

A JAMA Otolaryngology — Head & Neck Surgery study says polygenic risk scores associated with hearing loss in older adults is also associated with hearing decline in younger groups.

Genome-Wide Analysis Sheds Light on Genetics of ADHD

A genome-wide association study meta-analysis of attention-deficit hyperactivity disorder appearing in Nature Genetics links 76 genes to risk of having the disorder.

MicroRNA Cotargeting Linked to Lupus

A mouse-based study appearing in BMC Biology implicates two microRNAs with overlapping target sites in lupus.

Enzyme Involved in Lipid Metabolism Linked to Mutational Signatures

In Nature Genetics, a Wellcome Sanger Institute-led team found that APOBEC1 may contribute to the development of the SBS2 and SBS13 mutational signatures in the small intestine.