The evolving landscape of hybrid viral vector architectures: a persisting niche
- 1Laboratory of Genome Editing, Research Centre for Medical Genetics , ,
Abstract
The development of hybrid viral vectors was historically driven by the need to overcome inherent limitations of individual viral platforms, including restricted payload capacity, narrow tropism, and limited control over genomic persistence. By integrating functional modules from diverse viral and non-viral systems, these chimeric constructs exploit complementary mechanisms to expand therapeutic potential. This review examines the architectural principles underlying hybrid vector design, framing their evolution as a logical extension of viral engineering strategies - such as pseudotyping and genetic chimerization - rather than as a retrospective response to the rise of non-viral delivery platforms. We highlight key structural configurations, including adenoviral, lentiviral, herpes simplex virus (HSV) amplicon, baculoviral, and bacteriophage-derived chimeras, as well as their integration with transposon systems (e.g., Sleeping Beauty) to enable enhanced persistence and increased cargo capacity. In parallel, we analyze the biological and technological trade-offs associated with increased structural complexity, including manufacturing constraints, cumulative immunogenicity, and regulatory challenges. Collectively, hybrid vector systems represent a modular and evolving design paradigm that complements advances in monoplatform vectors and remains a valuable approach for addressing complex therapeutic challenges, for example those requiring expanded capacity, multifunctionality, or combinatorial control of gene delivery outcomes.
Related
- Navigating the rapidly evolving landscape of sequencing-based spatial transcriptomics technologies: a comprehensive multi-platform benchmark
- A protein–foldamer supramolecular synthon for self-assembled hybrid architectures
- The Evolving Bileome: A Pan-Repository Landscape of Expanded Bile Acid and Related Steroidal Signatures
- The Evolving Landscapes of Invisible Invaders: Global Insights on Plant Viruses and Vector Complexes.
- Stand and Landscape Drivers of Trap Captures of the Pine Wilt Disease Vector Monochamus alternatus (Coleoptera: Cerambycidae) in the Qinling Mountains
BibTeX
@article{kocherginnikitsky2026evolving,
title = {{The evolving landscape of hybrid viral vector architectures: a persisting niche}},
author = {Konstantin Kochergin-Nikitsky and Svetlana Smirnikhina},
journal = {Frontiers in bioengineering and biotechnology},
year = {2026},
month = oct,
doi = {10.3389/fbioe.2026.1900662},
url = {https://europepmc.org/article/PMC/PMC13720247},
note = {CC BY},
}
RIS
TY - JOUR
TI - The evolving landscape of hybrid viral vector architectures: a persisting niche
AU - Konstantin Kochergin-Nikitsky
AU - Svetlana Smirnikhina
PY - 2026
DA - 2026/10/16
JO - Frontiers in bioengineering and biotechnology
DO - 10.3389/fbioe.2026.1900662
UR - https://europepmc.org/article/PMC/PMC13720247
AB - The development of hybrid viral vectors was historically driven by the need to overcome inherent limitations of individual viral platforms, including restricted payload capacity, narrow tropism, and limited control over genomic persistence. By integrating functional modules from diverse viral and non-viral systems, these chimeric constructs exploit complementary mechanisms to expand therapeutic potential. This review examines the architectural principles underlying hybrid vector design, framing their evolution as a logical extension of viral engineering strategies - such as pseudotyping and genetic chimerization - rather than as a retrospective response to the rise of non-viral delivery platforms. We highlight key structural configurations, including adenoviral, lentiviral, herpes simplex virus (HSV) amplicon, baculoviral, and bacteriophage-derived chimeras, as well as their integration with transposon systems (e.g., Sleeping Beauty) to enable enhanced persistence and increased cargo capacity. In parallel, we analyze the biological and technological trade-offs associated with increased structural complexity, including manufacturing constraints, cumulative immunogenicity, and regulatory challenges. Collectively, hybrid vector systems represent a modular and evolving design paradigm that complements advances in monoplatform vectors and remains a valuable approach for addressing complex therapeutic challenges, for example those requiring expanded capacity, multifunctionality, or combinatorial control of gene delivery outcomes.
SN - 2296-4185
ER -