{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T21:27:02Z","timestamp":1783027622285,"version":"3.54.6"},"reference-count":120,"publisher":"Elsevier BV","issue":"3","license":[{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T00:00:00Z","timestamp":1769040000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000893","name":"Simons Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000893","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000025","name":"National Institute of Mental Health","doi-asserted-by":"publisher","award":["RM1MH138313"],"award-info":[{"award-number":["RM1MH138313"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009633","name":"National Institute of Child Health and Human Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cell.com","clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Trends in Neurosciences"],"published-print":{"date-parts":[[2026,3]]},"DOI":"10.1016\/j.tins.2026.01.008","type":"journal-article","created":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T05:22:37Z","timestamp":1772428957000},"page":"217-232","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":1,"title":["Challenges and opportunities in adapting high-throughput functional assays for in vivo neuroscience"],"prefix":"10.1016","volume":"49","author":[{"given":"Din","family":"Selmanovic","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5425-1476","authenticated-orcid":false,"given":"Joseph D.","family":"Dougherty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.tins.2026.01.008_bb0005","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1038\/nrg1836","article-title":"High-throughput RNAi screening in cultured cells: a user\u2019s guide","volume":"7","author":"Echeverri","year":"2006","journal-title":"Nat. Rev. Genet."},{"key":"10.1016\/j.tins.2026.01.008_bb0010","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1126\/science.1247005","article-title":"Genome-scale CRISPR-Cas9 knockout screening in human cells","volume":"343","author":"Shalem","year":"2014","journal-title":"Science"},{"key":"10.1016\/j.tins.2026.01.008_bb0015","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1016\/j.cell.2014.09.029","article-title":"Genome-scale CRISPR-mediated control of gene repression and activation","volume":"159","author":"Gilbert","year":"2014","journal-title":"Cell"},{"key":"10.1016\/j.tins.2026.01.008_bb0020","doi-asserted-by":"crossref","first-page":"1853","DOI":"10.1016\/j.cell.2016.11.038","article-title":"Perturb-seq: dissecting molecular circuits with scalable single-cell RNA profiling of pooled genetic screens","volume":"167","author":"Dixit","year":"2016","journal-title":"Cell"},{"key":"10.1016\/j.tins.2026.01.008_bb0025","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1038\/nmeth.4177","article-title":"Pooled CRISPR screening with single-cell transcriptome readout","volume":"14","author":"Datlinger","year":"2017","journal-title":"Nat. Methods"},{"key":"10.1016\/j.tins.2026.01.008_bb0030","doi-asserted-by":"crossref","DOI":"10.1126\/science.aaz6063","article-title":"In vivo Perturb-Seq reveals neuronal and glial abnormalities associated with autism risk genes","volume":"370","author":"Jin","year":"2020","journal-title":"Science"},{"key":"10.1016\/j.tins.2026.01.008_bb0035","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.1126\/science.1222794","article-title":"Systematic localization of common disease-associated variation in regulatory DNA","volume":"337","author":"Maurano","year":"2012","journal-title":"Science"},{"key":"10.1016\/j.tins.2026.01.008_bb0040","doi-asserted-by":"crossref","DOI":"10.1126\/science.adh0559","article-title":"Massively parallel characterization of regulatory elements in the developing human cortex","volume":"384","author":"Deng","year":"2024","journal-title":"Science"},{"key":"10.1016\/j.tins.2026.01.008_bb0045","doi-asserted-by":"crossref","DOI":"10.1126\/science.abi8654","article-title":"Functional regulatory variants implicate distinct transcriptional networks in dementia","volume":"377","author":"Cooper","year":"2022","journal-title":"Science"},{"key":"10.1016\/j.tins.2026.01.008_bb0050","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1038\/ng.3506","article-title":"Integrative approaches for large-scale transcriptome-wide association studies","volume":"48","author":"Gusev","year":"2016","journal-title":"Nat. Genet."},{"key":"10.1016\/j.tins.2026.01.008_bb0055","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1038\/nbt.2137","article-title":"Systematic dissection and optimization of inducible enhancers in human cells using a massively parallel reporter assay","volume":"30","author":"Melnikov","year":"2012","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.tins.2026.01.008_bb0060","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.ygeno.2015.06.005","article-title":"Decoding enhancers using massively parallel reporter assays","volume":"106","author":"Inoue","year":"2015","journal-title":"Genomics"},{"key":"10.1016\/j.tins.2026.01.008_bb0065","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.1016\/j.cell.2016.04.027","article-title":"Direct identification of hundreds of expression-modulating variants using a multiplexed reporter assay","volume":"165","author":"Tewhey","year":"2016","journal-title":"Cell"},{"key":"10.1016\/j.tins.2026.01.008_bb0070","article-title":"Active learning of enhancers and silencers in the developing neural retina","volume":"16","author":"Friedman","year":"2025","journal-title":"Cell Syst."},{"key":"10.1016\/j.tins.2026.01.008_bb0075","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.41279","article-title":"Synthetic and genomic regulatory elements reveal aspects of cis-regulatory grammar in mouse embryonic stem cells","volume":"9","author":"King","year":"2020","journal-title":"ELife"},{"key":"10.1016\/j.tins.2026.01.008_bb0080","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1038\/s41588-019-0455-2","article-title":"High-throughput identification of human SNPs affecting regulatory element activity","volume":"51","author":"van Arensbergen","year":"2019","journal-title":"Nat. Genet."},{"key":"10.1016\/j.tins.2026.01.008_bb0085","doi-asserted-by":"crossref","DOI":"10.1016\/j.xgen.2023.100404","article-title":"Systematic investigation of allelic regulatory activity of schizophrenia-associated common variants","volume":"3","author":"McAfee","year":"2023","journal-title":"Cell Genomics"},{"key":"10.1016\/j.tins.2026.01.008_bb0090","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1016\/j.cell.2024.12.022","article-title":"Massively parallel reporter assay investigates shared genetic variants of eight psychiatric disorders","volume":"188","author":"Lee","year":"2025","journal-title":"Cell"},{"key":"10.1016\/j.tins.2026.01.008_bb0095","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1038\/nmeth.4534","article-title":"Resolving systematic errors in widely used enhancer activity assays in human cells","volume":"15","author":"Muerdter","year":"2018","journal-title":"Nat. Methods"},{"key":"10.1016\/j.tins.2026.01.008_bb0100","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.45396","article-title":"Translation affects mRNA stability in a codon-dependent manner in human cells","volume":"8","author":"Wu","year":"2019","journal-title":"ELife"},{"key":"10.1016\/j.tins.2026.01.008_bb0105","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1016\/j.cell.2015.02.029","article-title":"Codon optimality is a major determinant of mRNA stability","volume":"160","author":"Presnyak","year":"2015","journal-title":"Cell"},{"key":"10.1016\/j.tins.2026.01.008_bb0110","article-title":"Approaches for identification of 5\u2032 UTR mutations impacting translation and protein production from neurodevelopmental disorder genes","volume":"5","author":"Plassmeyer","year":"2025","journal-title":"Cell Rep. Methods"},{"key":"10.1016\/j.tins.2026.01.008_bb0115","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1038\/s41592-024-02260-3","article-title":"Multiplex profiling of developmental cis-regulatory elements with quantitative single-cell expression reporters","volume":"21","author":"Lalanne","year":"2024","journal-title":"Nat. Methods"},{"key":"10.1016\/j.tins.2026.01.008_bb0120","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1038\/s41587-019-0164-5","article-title":"Human 5\u2032 UTR design and variant effect prediction from a massively parallel translation assay","volume":"37","author":"Sample","year":"2019","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.tins.2026.01.008_bb0125","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.74207","article-title":"Temporal analysis of enhancers during mouse cerebellar development reveals dynamic and novel regulatory functions","volume":"11","author":"Ramirez","year":"2022","journal-title":"ELife"},{"key":"10.1016\/j.tins.2026.01.008_bb0130","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1016\/j.cell.2012.12.041","article-title":"A high-resolution enhancer atlas of the developing telencephalon","volume":"152","author":"Visel","year":"2013","journal-title":"Cell"},{"key":"10.1016\/j.tins.2026.01.008_bb0135","doi-asserted-by":"crossref","first-page":"1521","DOI":"10.1016\/j.cell.2013.11.033","article-title":"Rapid and pervasive changes in genome-wide enhancer usage during mammalian development","volume":"155","author":"Nord","year":"2013","journal-title":"Cell"},{"key":"10.1016\/j.tins.2026.01.008_bb0140","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1038\/s41398-020-00953-9","article-title":"Common genetic risk variants identified in the SPARK cohort support DDHD2 as a candidate risk gene for autism","volume":"10","author":"Matoba","year":"2020","journal-title":"Transl. Psychiatry"},{"key":"10.1016\/j.tins.2026.01.008_bb0145","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1038\/s41398-021-01493-6","article-title":"Transcriptional-regulatory convergence across functional MDD risk variants identified by massively parallel reporter assays","volume":"11","author":"Mulvey","year":"2021","journal-title":"Transl. Psychiatry"},{"key":"10.1016\/j.tins.2026.01.008_bb0150","article-title":"Massively parallel assessment of gene regulatory activity at human cortical structure associated variants","author":"Matoba","year":"2025","journal-title":"bioRxiv"},{"key":"10.1016\/j.tins.2026.01.008_bb0155","doi-asserted-by":"crossref","first-page":"3583","DOI":"10.1038\/s41467-019-11526-w","article-title":"Saturation mutagenesis of twenty disease-associated regulatory elements at single base-pair resolution","volume":"10","author":"Kircher","year":"2019","journal-title":"Nat. Commun."},{"key":"10.1016\/j.tins.2026.01.008_bb0160","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1016\/j.stem.2019.09.010","article-title":"Identification and massively parallel characterization of regulatory elements driving neural induction","volume":"25","author":"Inoue","year":"2019","journal-title":"Cell Stem Cell"},{"key":"10.1016\/j.tins.2026.01.008_bb0165","article-title":"A massively parallel reporter assay dissects the influence of chromatin structure on cis-regulatory activity","author":"Maricque","year":"2018","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.tins.2026.01.008_bb0170","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1101\/gr.193789.115","article-title":"Massively parallel cis-regulatory analysis in the mammalian central nervous system","volume":"26","author":"Shen","year":"2016","journal-title":"Genome Res."},{"key":"10.1016\/j.tins.2026.01.008_bb0175","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1038\/s41467-017-02745-0","article-title":"PTRE-seq reveals mechanism and interactions of RNA binding proteins and miRNAs","volume":"9","author":"Cottrell","year":"2018","journal-title":"Nat. Commun."},{"key":"10.1016\/j.tins.2026.01.008_bb0180","doi-asserted-by":"crossref","first-page":"6844","DOI":"10.1038\/s41467-025-62000-9","article-title":"U-rich elements drive pervasive cryptic splicing in 3\u2032 UTR massively parallel reporter assays","volume":"16","author":"Dao","year":"2025","journal-title":"Nat. Commun."},{"key":"10.1016\/j.tins.2026.01.008_bb0185","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1038\/s42003-023-05483-w","article-title":"A Cre-dependent massively parallel reporter assay allows for cell-type specific assessment of the functional effects of non-coding elements in vivo","volume":"6","author":"Lagunas","year":"2023","journal-title":"Commun. Biol."},{"key":"10.1016\/j.tins.2026.01.008_bb0190","doi-asserted-by":"crossref","first-page":"10898","DOI":"10.1038\/s41467-024-55274-y","article-title":"NaP-TRAP reveals the regulatory grammar in 5\u2032UTR-mediated translation regulation during zebrafish development","volume":"15","author":"Strayer","year":"2024","journal-title":"Nat. Commun."},{"key":"10.1016\/j.tins.2026.01.008_bb0195","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1038\/s41593-021-00862-0","article-title":"Genome-wide CRISPRi\/a screens in human neurons link lysosomal failure to ferroptosis","volume":"24","author":"Tian","year":"2021","journal-title":"Nat. Neurosci."},{"key":"10.1016\/j.tins.2026.01.008_bb0200","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.neuron.2019.07.014","article-title":"CRISPR interference-based platform for multimodal genetic screens in human iPSC-derived neurons","volume":"104","author":"Tian","year":"2019","journal-title":"Neuron"},{"key":"10.1016\/j.tins.2026.01.008_bb0205","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1016\/j.celrep.2019.03.047","article-title":"Genome-wide CRISPR-Cas9 screens expose genetic vulnerabilities and mechanisms of temozolomide sensitivity in glioblastoma stem cells","volume":"27","author":"MacLeod","year":"2019","journal-title":"Cell Rep."},{"key":"10.1016\/j.tins.2026.01.008_bb0210","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1038\/s41593-022-01131-4","article-title":"A CRISPRi\/a platform in human iPSC-derived microglia uncovers regulators of disease states","volume":"25","author":"Dr\u00e4ger","year":"2022","journal-title":"Nat. Neurosci."},{"key":"10.1016\/j.tins.2026.01.008_bb0215","doi-asserted-by":"crossref","first-page":"9527","DOI":"10.1073\/pnas.1900867116","article-title":"Genome-wide CRISPR screen for Zika virus resistance in human neural cells","volume":"116","author":"Li","year":"2019","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.tins.2026.01.008_bb0220","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1038\/s41586-023-06570-y","article-title":"Transcriptional linkage analysis with in vivo AAV-Perturb-seq","volume":"622","author":"Santinha","year":"2023","journal-title":"Nature"},{"key":"10.1016\/j.tins.2026.01.008_bb0225","doi-asserted-by":"crossref","first-page":"3236","DOI":"10.1016\/j.cell.2024.04.050","article-title":"Massively parallel in vivo Perturb-seq reveals cell-type-specific transcriptional networks in cortical development","volume":"187","author":"Zheng","year":"2024","journal-title":"Cell"},{"key":"10.1016\/j.tins.2026.01.008_bb0230","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1038\/s41592-020-0837-5","article-title":"Targeted Perturb-seq enables genome-scale genetic screens in single cells","volume":"17","author":"Schraivogel","year":"2020","journal-title":"Nat. Methods"},{"key":"10.1016\/j.tins.2026.01.008_bb0235","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1038\/s41586-022-05279-8","article-title":"Inferring and perturbing cell fate regulomes in human brain organoids","volume":"621","author":"Fleck","year":"2023","journal-title":"Nature"},{"key":"10.1016\/j.tins.2026.01.008_bb0240","doi-asserted-by":"crossref","first-page":"1528","DOI":"10.1038\/s41593-022-01180-9","article-title":"CRISPRi screens in human iPSC-derived astrocytes elucidate regulators of distinct inflammatory reactive states","volume":"25","author":"Leng","year":"2022","journal-title":"Nat. Neurosci."},{"key":"10.1016\/j.tins.2026.01.008_bb0245","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1038\/s41586-023-06473-y","article-title":"Single-cell brain organoid screening identifies developmental defects in autism","volume":"621","author":"Li","year":"2023","journal-title":"Nature"},{"key":"10.1016\/j.tins.2026.01.008_bb0250","doi-asserted-by":"crossref","first-page":"1302","DOI":"10.1038\/s41467-021-21478-9","article-title":"Combinatorial CRISPR screen identifies fitness effects of gene paralogues","volume":"12","author":"Thompson","year":"2021","journal-title":"Nat. Commun."},{"key":"10.1016\/j.tins.2026.01.008_bb0255","doi-asserted-by":"crossref","first-page":"3577","DOI":"10.1038\/s41467-024-47795-3","article-title":"Efficient gene knockout and genetic interaction screening using the in4mer CRISPR\/Cas12a multiplex knockout platform","volume":"15","author":"Esmaeili Anvar","year":"2024","journal-title":"Nat. Commun."},{"key":"10.1016\/j.tins.2026.01.008_bb0260","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1016\/j.cell.2018.06.010","article-title":"Mapping the genetic landscape of human cells","volume":"174","author":"Horlbeck","year":"2018","journal-title":"Cell"},{"key":"10.1016\/j.tins.2026.01.008_bb0265","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1126\/science.aax4438","article-title":"Exploring genetic interaction manifolds constructed from rich single-cell phenotypes","volume":"365","author":"Norman","year":"2019","journal-title":"Science"},{"key":"10.1016\/j.tins.2026.01.008_bb0270","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1038\/nbt.4062","article-title":"Dual gene activation and knockout screen reveals directional dependencies in genetic networks","volume":"36","author":"Boettcher","year":"2018","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.tins.2026.01.008_bb0275","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.neuron.2020.01.004","article-title":"Genome-wide in vivo CNS screening identifies genes that modify CNS neuronal survival and mHTT toxicity","volume":"106","author":"Wertz","year":"2020","journal-title":"Neuron"},{"key":"10.1016\/j.tins.2026.01.008_bb0280","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1126\/science.aag2445","article-title":"Systematic mapping of functional enhancer\u2013promoter connections with CRISPR interference","volume":"354","author":"Fulco","year":"2016","journal-title":"Science"},{"key":"10.1016\/j.tins.2026.01.008_bb0285","doi-asserted-by":"crossref","first-page":"2503","DOI":"10.1016\/j.cell.2021.03.025","article-title":"Genome-wide programmable transcriptional memory by CRISPR-based epigenome editing","volume":"184","author":"Nu\u00f1ez","year":"2021","journal-title":"Cell"},{"key":"10.1016\/j.tins.2026.01.008_bb0290","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1038\/s41589-020-0480-6","article-title":"Deep mutational scanning reveals the structural basis for \u03b1-synuclein activity","volume":"16","author":"Newberry","year":"2020","journal-title":"Nat. Chem. Biol."},{"key":"10.1016\/j.tins.2026.01.008_bb0295","article-title":"Deep mutational scanning of proteins in mammalian cells","volume":"3","author":"Maes","year":"2023","journal-title":"Cell Rep. Methods"},{"key":"10.1016\/j.tins.2026.01.008_bb0300","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1016\/j.cell.2021.01.012","article-title":"Massively parallel assessment of human variants with base editor screens","volume":"184","author":"Hanna","year":"2021","journal-title":"Cell"},{"key":"10.1016\/j.tins.2026.01.008_bb0305","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.69479","article-title":"Parallel functional testing identifies enhancers active in early postnatal mouse brain","volume":"10","author":"Lambert","year":"2021","journal-title":"ELife"},{"key":"10.1016\/j.tins.2026.01.008_bb0310","doi-asserted-by":"crossref","first-page":"4786","DOI":"10.1038\/s41467-025-60064-1","article-title":"Massively parallel reporter assays and mouse transgenic assays provide correlated and complementary information about neuronal enhancer activity","volume":"16","author":"Kosicki","year":"2025","journal-title":"Nat. Commun."},{"key":"10.1016\/j.tins.2026.01.008_bb0315","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1038\/nn.4494","article-title":"Neuronal activity modifies the chromatin accessibility landscape in the adult brain","volume":"20","author":"Su","year":"2017","journal-title":"Nat. Neurosci."},{"key":"10.1016\/j.tins.2026.01.008_bb0320","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1111\/jnc.14103","article-title":"Molecular mechanisms of experience-dependent maturation in cortical GABAergic inhibition","volume":"142","author":"Begum","year":"2017","journal-title":"J. Neurochem."},{"key":"10.1016\/j.tins.2026.01.008_bb0325","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1016\/j.neuron.2020.06.008","article-title":"An activity-mediated transition in transcription in early postnatal neurons","volume":"107","author":"Stroud","year":"2020","journal-title":"Neuron"},{"key":"10.1016\/j.tins.2026.01.008_bb0330","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1007\/s40259-017-0234-5","article-title":"Adeno-associated virus (AAV) as a vector for gene therapy","volume":"31","author":"Naso","year":"2017","journal-title":"BioDrugs"},{"key":"10.1016\/j.tins.2026.01.008_bb0335","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.brainres.2007.11.015","article-title":"Specific AAV serotypes stably transduce primary hippocampal and cortical cultures with high efficiency and low toxicity","volume":"1190","author":"Royo","year":"2008","journal-title":"Brain Res."},{"key":"10.1016\/j.tins.2026.01.008_bb0340","doi-asserted-by":"crossref","first-page":"1528","DOI":"10.1038\/sj.gt.3302011","article-title":"Recombinant AAV serotype 1 transduction efficiency and tropism in the murine brain","volume":"10","author":"Wang","year":"2003","journal-title":"Gene Ther."},{"key":"10.1016\/j.tins.2026.01.008_bb0345","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.neulet.2014.05.044","article-title":"Widespread neuron-specific transgene expression in brain and spinal cord following synapsin promoter-driven AAV9 neonatal intracerebroventricular injection","volume":"576","author":"McLean","year":"2014","journal-title":"Neurosci. Lett."},{"key":"10.1016\/j.tins.2026.01.008_bb0350","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/j.omtm.2020.10.011","article-title":"CNS transduction benefits of AAV-PHP.eB over AAV9 are dependent on administration route and mouse strain","volume":"19","author":"Mathiesen","year":"2020","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"10.1016\/j.tins.2026.01.008_bb0355","doi-asserted-by":"crossref","first-page":"1963","DOI":"10.3390\/cells13231963","article-title":"Synthetic promoters in gene therapy: design approaches, features and applications","volume":"13","author":"Artemyev","year":"2024","journal-title":"Cells"},{"key":"10.1016\/j.tins.2026.01.008_bb0360","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1038\/s41586-021-03465-8","article-title":"Comparative cellular analysis of motor cortex in human, marmoset and mouse","volume":"598","author":"Bakken","year":"2021","journal-title":"Nature"},{"key":"10.1016\/j.tins.2026.01.008_bb0365","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1038\/s41593-022-01022-8","article-title":"Dissection of artifactual and confounding glial signatures by single-cell sequencing of mouse and human brain","volume":"25","author":"Marsh","year":"2022","journal-title":"Nat. Neurosci."},{"key":"10.1016\/j.tins.2026.01.008_bb0370","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1016\/j.biopsych.2023.02.009","article-title":"Sex significantly impacts the function of major depression\u2013linked variants in vivo","volume":"94","author":"Mulvey","year":"2023","journal-title":"Biol. Psychiatry"},{"key":"10.1016\/j.tins.2026.01.008_bb0375","doi-asserted-by":"crossref","DOI":"10.3389\/fgene.2025.1533900","article-title":"An in vivo systemic massively parallel platform for deciphering animal tissue-specific regulatory function","volume":"16","author":"Brown","year":"2025","journal-title":"Front. Genet."},{"key":"10.1016\/j.tins.2026.01.008_bb0380","doi-asserted-by":"crossref","first-page":"2129","DOI":"10.1038\/s41593-025-02043-9","article-title":"CRISPR screening by AAV episome-sequencing (CrAAVe-seq): a scalable cell-type-specific in vivo platform uncovers neuronal essential genes","volume":"28","author":"Ramani","year":"2025","journal-title":"Nat. Neurosci."},{"key":"10.1016\/j.tins.2026.01.008_bb0385","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.virol.2007.10.007","article-title":"Tropism and toxicity of adeno-associated viral vector serotypes 1, 2, 5, 6, 7, 8, and 9 in rat neurons and glia in vitro","volume":"372","author":"Howard","year":"2008","journal-title":"Virology"},{"key":"10.1016\/j.tins.2026.01.008_bb0390","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.48089","article-title":"A scalable platform for the development of cell-type-specific viral drivers","volume":"8","author":"Hrvatin","year":"2019","journal-title":"ELife"},{"key":"10.1016\/j.tins.2026.01.008_bb0395","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1038\/s41587-025-02565-4","article-title":"Spatial genomics of AAV vectors reveals mechanism of transcriptional crosstalk that enables targeted delivery of large genetic cargo","volume":"44","author":"Coughlin","year":"2026","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.tins.2026.01.008_bb0400","article-title":"Technical and biological sources of noise confound multiplexed enhancer AAV screening","author":"Hunker","year":"2025","journal-title":"bioRxiv"},{"key":"10.1016\/j.tins.2026.01.008_bb0405","doi-asserted-by":"crossref","first-page":"1172","DOI":"10.1038\/nn.4593","article-title":"Engineered AAVs for efficient noninvasive gene delivery to the central and peripheral nervous systems","volume":"20","author":"Chan","year":"2017","journal-title":"Nat. Neurosci."},{"key":"10.1016\/j.tins.2026.01.008_bb0410","doi-asserted-by":"crossref","DOI":"10.1016\/j.isci.2024.109777","article-title":"New AAV9 engineered variants with enhanced neurotropism and reduced liver off-targeting in mice and marmosets","volume":"27","author":"Giannelli","year":"2024","journal-title":"iScience"},{"key":"10.1016\/j.tins.2026.01.008_bb0415","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1016\/j.neuron.2016.09.021","article-title":"A designer AAV variant permits efficient retrograde access to projection neurons","volume":"92","author":"Tervo","year":"2016","journal-title":"Neuron"},{"key":"10.1016\/j.tins.2026.01.008_bb0420","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1038\/s41593-021-00969-4","article-title":"AAV capsid variants with brain-wide transgene expression and decreased liver targeting after intravenous delivery in mouse and marmoset","volume":"25","author":"Goertsen","year":"2022","journal-title":"Nat. Neurosci."},{"key":"10.1016\/j.tins.2026.01.008_bb0425","doi-asserted-by":"crossref","DOI":"10.1523\/ENEURO.0391-24.2024","article-title":"Comparative analysis of six adeno-associated viral vector serotypes in mouse inferior colliculus and cerebellum","volume":"11","author":"Witteveen","year":"2024","journal-title":"eNeuro"},{"key":"10.1016\/j.tins.2026.01.008_bb0430","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1038\/gt.2016.11","article-title":"Exosome-associated AAV vector as a robust and convenient neuroscience tool","volume":"23","author":"Hudry","year":"2016","journal-title":"Gene Ther."},{"key":"10.1016\/j.tins.2026.01.008_bb0435","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0076310","article-title":"Analysis of transduction efficiency, tropism and axonal transport of AAV serotypes 1, 2, 5, 6, 8, and 9 in the mouse brain","volume":"8","author":"Aschauer","year":"2013","journal-title":"PLoS One"},{"key":"10.1016\/j.tins.2026.01.008_bb0440","doi-asserted-by":"crossref","DOI":"10.1016\/j.omtm.2025.101494","article-title":"Common AAV gene therapy vectors show nonselective transduction of ex vivo human brain tissue","volume":"33","author":"McGinnis","year":"2025","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"10.1016\/j.tins.2026.01.008_bb0445","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1089\/humc.2019.030","article-title":"The influence of murine genetic background in adeno-associated virus transduction of the mouse brain","volume":"30","author":"He","year":"2019","journal-title":"Hum. Gene Ther. Clin. Dev."},{"key":"10.1016\/j.tins.2026.01.008_bb0450","doi-asserted-by":"crossref","first-page":"800","DOI":"10.1101\/gr.144899.112","article-title":"Systematic dissection of regulatory motifs in 2000 predicted human enhancers using a massively parallel reporter assay","volume":"23","author":"Kheradpour","year":"2013","journal-title":"Genome Res."},{"key":"10.1016\/j.tins.2026.01.008_bb0455","doi-asserted-by":"crossref","first-page":"1504","DOI":"10.1038\/s41467-022-28659-0","article-title":"Massively parallel reporter perturbation assays uncover temporal regulatory architecture during neural differentiation","volume":"13","author":"Kreimer","year":"2022","journal-title":"Nat. Commun."},{"key":"10.1016\/j.tins.2026.01.008_bb0460","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1101\/gr.277204.122","article-title":"Challenges and considerations for reproducibility of STARR-seq assays","volume":"33","author":"Das","year":"2023","journal-title":"Genome Res."},{"key":"10.1016\/j.tins.2026.01.008_bb0465","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1007\/978-1-0716-4220-7_15","article-title":"Combining oligo pools and golden gate cloning to create protein variant libraries or guide RNA libraries for CRISPR applications","volume":"2850","author":"Maci\u00e1 Valero","year":"2025","journal-title":"Methods Mol. Biol."},{"key":"10.1016\/j.tins.2026.01.008_bb0470","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1186\/1741-7007-12-42","article-title":"RNA-seq: impact of RNA degradation on transcript quantification","volume":"12","author":"Gallego Romero","year":"2014","journal-title":"BMC Biol."},{"key":"10.1016\/j.tins.2026.01.008_bb0475","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1038\/mt.2016.11","article-title":"Genome-wide profiling reveals remarkable parallels between insertion site selection properties of the MLV retrovirus and the piggyBac transposon in primary human CD4+ T cells","volume":"24","author":"Gogol-D\u00f6ring","year":"2016","journal-title":"Mol. Ther."},{"key":"10.1016\/j.tins.2026.01.008_bb0480","doi-asserted-by":"crossref","first-page":"9601","DOI":"10.1038\/s41467-024-54059-7","article-title":"Predicting synthetic mRNA stability using massively parallel kinetic measurements, biophysical modeling, and machine learning","volume":"15","author":"Cetnar","year":"2024","journal-title":"Nat. Commun."},{"key":"10.1016\/j.tins.2026.01.008_bb0485","doi-asserted-by":"crossref","first-page":"1536","DOI":"10.1038\/s41467-022-28776-w","article-title":"Combinatorial optimization of mRNA structure, stability, and translation for RNA-based therapeutics","volume":"13","author":"Leppek","year":"2022","journal-title":"Nat. Commun."},{"key":"10.1016\/j.tins.2026.01.008_bb0490","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.1111\/ejn.12126","article-title":"Viral transduction of the neonatal brain delivers controllable genetic mosaicism for visualising and manipulating neuronal circuits in vivo","volume":"37","author":"Kim","year":"2013","journal-title":"Eur. J. Neurosci."},{"key":"10.1016\/j.tins.2026.01.008_bb0495","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.1038\/mt.2011.72","article-title":"Preclinical differences of intravascular AAV9 delivery to neurons and glia: a comparative study of adult mice and nonhuman primates","volume":"19","author":"Gray","year":"2011","journal-title":"Mol. Ther."},{"key":"10.1016\/j.tins.2026.01.008_bb0500","doi-asserted-by":"crossref","DOI":"10.1016\/j.omtm.2023.08.021","article-title":"High-titer AAV disrupts cerebrovascular integrity and induces lymphocyte infiltration in adult mouse brain","volume":"31","author":"Guo","year":"2023","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"10.1016\/j.tins.2026.01.008_bb0505","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1089\/hum.2010.245","article-title":"Optimizing promoters for recombinant adeno-associated virus-mediated gene expression in the peripheral and central nervous system using self-complementary vectors","volume":"22","author":"Gray","year":"2011","journal-title":"Hum. Gene Ther."},{"key":"10.1016\/j.tins.2026.01.008_bb0510","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0010611","article-title":"Systematic comparison of constitutive promoters and the doxycycline-inducible promoter","volume":"5","author":"Qin","year":"2010","journal-title":"PLoS One"},{"key":"10.1016\/j.tins.2026.01.008_bb0515","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1016\/j.cels.2024.11.003","article-title":"Optimized reporters for multiplexed detection of transcription factor activity","volume":"15","author":"Trauernicht","year":"2024","journal-title":"Cell Syst."},{"key":"10.1016\/j.tins.2026.01.008_bb0520","doi-asserted-by":"crossref","first-page":"10003","DOI":"10.1073\/pnas.1918241117","article-title":"A viral toolkit for recording transcription factor\u2013DNA interactions in live mouse tissues","volume":"117","author":"Cammack","year":"2020","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.tins.2026.01.008_bb0525","doi-asserted-by":"crossref","first-page":"2886","DOI":"10.1128\/JVI.73.4.2886-2892.1999","article-title":"Woodchuck hepatitis virus posttranscriptional regulatory element enhances expression of transgenes delivered by retroviral vectors","volume":"73","author":"Zufferey","year":"1999","journal-title":"J. Virol."},{"key":"10.1016\/j.tins.2026.01.008_bb0530","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1038\/s41587-019-0090-6","article-title":"Highly efficient expression of circular RNA aptamers in cells using autocatalytic transcripts","volume":"37","author":"Litke","year":"2019","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.tins.2026.01.008_bb0535","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.cell.2018.11.029","article-title":"A genome-wide framework for mapping gene regulation via cellular genetic screens","volume":"176","author":"Gasperini","year":"2019","journal-title":"Cell"},{"key":"10.1016\/j.tins.2026.01.008_bb0540","doi-asserted-by":"crossref","first-page":"8356","DOI":"10.1038\/s41598-022-12404-0","article-title":"Identification of adeno-associated virus variants for gene transfer into human neural cell types by parallel capsid screening","volume":"12","author":"Flitsch","year":"2022","journal-title":"Sci. Rep."},{"key":"10.1016\/j.tins.2026.01.008_bb0545","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1038\/nbt.1515","article-title":"Intravascular AAV9 preferentially targets neonatal neurons and adult astrocytes","volume":"27","author":"Foust","year":"2009","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.tins.2026.01.008_bb0550","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1016\/j.cell.2008.10.028","article-title":"A translational profiling approach for the molecular characterization of CNS cell types","volume":"135","author":"Heiman","year":"2008","journal-title":"Cell"},{"key":"10.1016\/j.tins.2026.01.008_bb0555","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1016\/j.cell.2008.10.029","article-title":"Application of a translational profiling approach for the comparative analysis of CNS cell types","volume":"135","author":"Doyle","year":"2008","journal-title":"Cell"},{"key":"10.1016\/j.tins.2026.01.008_bb0560","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1038\/s41588-022-01278-7","article-title":"A single-cell massively parallel reporter assay detects cell-type-specific gene regulation","volume":"55","author":"Zhao","year":"2023","journal-title":"Nat. Genet."},{"key":"10.1016\/j.tins.2026.01.008_bb0565","doi-asserted-by":"crossref","DOI":"10.1126\/sciadv.adw0730","article-title":"Lipid nanoparticles for mRNA delivery in brain via systemic administration","volume":"11","author":"Cao","year":"2025","journal-title":"Sci. Adv."},{"key":"10.1016\/j.tins.2026.01.008_bb0570","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1038\/nbt.1807","article-title":"Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes","volume":"29","author":"Alvarez-Erviti","year":"2011","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.tins.2026.01.008_bb0575","doi-asserted-by":"crossref","DOI":"10.1002\/advs.201700611","article-title":"Exosome\u2013liposome hybrid nanoparticles deliver CRISPR\/Cas9 system in MSCs","volume":"5","author":"Lin","year":"2018","journal-title":"Adv. Sci."},{"key":"10.1016\/j.tins.2026.01.008_bb0580","doi-asserted-by":"crossref","DOI":"10.1016\/j.device.2025.100894","article-title":"Acoustic emissions dose and spatial control of blood\u2013brain barrier opening with focused ultrasound","volume":"3","author":"Woodworth","year":"2025","journal-title":"Device"},{"key":"10.1016\/j.tins.2026.01.008_bb0585","article-title":"Extensive length and homology dependent chimerism in pool-packaged AAV libraries","author":"Lalanne","year":"2025","journal-title":"bioRxiv"},{"key":"10.1016\/j.tins.2026.01.008_bb0590","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1038\/nmeth.4604","article-title":"On the design of CRISPR-based single-cell molecular screens","volume":"15","author":"Hill","year":"2018","journal-title":"Nat. Methods"},{"key":"10.1016\/j.tins.2026.01.008_bb0595","doi-asserted-by":"crossref","first-page":"2141","DOI":"10.1016\/j.cell.2025.02.012","article-title":"Simultaneous CRISPR screening and spatial transcriptomics reveal intracellular, intercellular, and functional transcriptional circuits","volume":"188","author":"Binan","year":"2025","journal-title":"Cell"},{"key":"10.1016\/j.tins.2026.01.008_bb0600","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1038\/s41586-019-1049-y","article-title":"Transcriptome-scale super-resolved imaging in tissues by RNA seqFISH+","volume":"568","author":"Eng","year":"2019","journal-title":"Nature"}],"container-title":["Trends in Neurosciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0166223626000111?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0166223626000111?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T21:08:46Z","timestamp":1783026526000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0166223626000111"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3]]},"references-count":120,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,3]]}},"alternative-id":["S0166223626000111"],"URL":"https:\/\/doi.org\/10.1016\/j.tins.2026.01.008","relation":{},"ISSN":["0166-2236"],"issn-type":[{"value":"0166-2236","type":"print"}],"subject":[],"published":{"date-parts":[[2026,3]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Challenges and opportunities in adapting high-throughput functional assays for in vivo neuroscience","name":"articletitle","label":"Article Title"},{"value":"Trends in Neurosciences","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.tins.2026.01.008","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 The Author(s). Published by Elsevier Ltd.","name":"copyright","label":"Copyright"}]}}