Evidence map›Paper›PMID 40849411›Full record

ArticleNature communications2025

Modeling integration site data for safety assessment with MELISSA.

Tsai-Yu Lin, Giacomo Ceoldo, Kimberley House, Matthew Welty, Thao Thi Dang, Denise Klatt, Christian Brendel, Michael P Murphy, Kenneth Cornetta, Danilo Pellin

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Trial
  2. Article
  3. Article
  4. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Tsai-Yu Lin *National Gene Vector Biorepository, Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.ORCID http://orcid.org/0000-0002-8076-1584
Giacomo Ceoldo *Division of Hematology/Oncology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-3600-1043
Kimberley HouseNational Gene Vector Biorepository, Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.
Matthew WeltyNational Gene Vector Biorepository, Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.
Thao Thi DangNational Gene Vector Biorepository, Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.
Denise KlattDivision of Hematology/Oncology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Christian BrendelDivision of Hematology/Oncology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0003-4081-4351
Michael P MurphyDepartment of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA.
Kenneth CornettaNational Gene Vector Biorepository, Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.ORCID http://orcid.org/0000-0003-1415-3668
Danilo PellinDivision of Hematology/Oncology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. danilo_pellin@dfci.harvard.edu.ORCID http://orcid.org/0000-0002-2647-0508

Funding

Tumor Microenvironment and Metastasis ProgramP30CA082709 · NCI · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI David W Clapp · 1999 to 2026
$59.3M
PURPOSE OF THE NGVB CONTRACT IS TO CONTINUE SUPPORTING GENE THERAPY RESEARCH.75N92019D00018 · OD · INDIANA UNIVERSITY INDIANAPOLIS · 2019 to 2023
$1.7M
NCI NIH HHS P30 CA082709NHLBI NIH HHS 75N92019D00018
6 · The paper itself

Abstract

Gene and cell therapies pose safety concerns due to potential insertional mutagenesis by viral vectors. We introduce MELISSA, a regression-based statistical framework for analyzing Integration Site (IS) data to assess insertional mutagenesis risk, by estimating and comparing gene-specific integration rates and their impact on clone fitness. We characterized the IS profile of a lentiviral vector on Mesenchymal Stem Cells (MSCs) and compared it with that of Hematopoietic Stem and Progenitor Cells (HSPCs). We applied MELISSA to published IS data from patients enrolled in gene therapy clinical trials, successfully identifying both known and novel genes that drive changes in clone growth through vector integration. MELISSA offers a quantitative tool to bridge the gap between IS data and safety and efficacy evaluation, facilitating the generation of comprehensive data packages supporting Investigational New Drug (IND) and Biologics License (BLA) applications and the development of safe and effective gene and cell therapies.

Indexed as

Genetic TherapyMutagenesis, InsertionalGenetic VectorsHematopoietic Stem CellsHumansLentivirusMesenchymal Stem Cells

Identifiers

PMID40849411
PMCPMC12375041

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.