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Engineering Linear Cap-independent mRNA Vaccines with Intrinsic 1 Adjuvanticity for Potent Cancer Immunotherapy

ABSTRACT: We present 25 a streamlined linear cap-independent RNA (LciRNA) cancer vaccine platform that achieves stable 26 expression in vivo without 5’ capping or ribonucleotide modification, and innately stimulates 27 immune responses to enhance antitumor immunity. By fusing a UPA protective sequence, composed 28 of a viral exoribonuclease-resistant RNA (xrRNA) and a poly(A) binding protein (PABP) motif, 29 with an optimized Enterovirus A internal ribosome entry site, LciRNA resists 5’ exonuclease decay 30 and drives superior in vivo expression.

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ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Hela Cell

SUBMITTER: Shenglin Huang

LAB HEAD: Shenglin Huang

PROVIDER: PXD067836 | Pride | 2026-01-26

REPOSITORIES: Pride

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Project description:Current human reproductive risk assessment methods rely on semen and serum hormone analyses, which are not easily comparable to the histopathological endpoints and mating studies used in animal testing. Because of these limitations, there is a need to develop universal evaluations that reliably reflect male reproductive function. We hypothesized that toxicant-induced testicular injury can be detected in sperm using mRNA transcripts as indicators of insult. To test this, we exposed adult male Fischer 344 rats to low doses of model testicular toxicants and classically characterized the testicular injury while simultaneously evaluating sperm mRNA transcripts from the same animals. Overall, this study aimed to: 1) identify sperm transcripts altered after exposure to the model testicular toxicant, 2,5-hexanedione (HD) using microarrays; 2) expand on the HD-induced transcript changes in a comprehensive time course experiment using qRT-PCR arrays; and 3) test these injury indicators after exposure to another model testicular toxicant, carbendazim (CBZ). Microarray analysis of HD-treated adult Fischer 344 rats identified 128 altered sperm mRNA transcripts when compared to control using linear models of microarray analysis (q < 0.05). All transcript alterations disappeared after 3 months of post-exposure recovery. In the time course experiment, time-dependent alterations were observed for 12 candidate transcripts selected from the microarray data based upon fold change and biological relevance, and 8 of these transcripts remained significantly altered after the 3-month recovery period (p < 0.05). In the last experiment, 8 candidate transcripts changed after exposure to CBZ (p < 0.05). The two testicular toxicants produced distinct molecular signatures with only 4 overlapping transcripts between them, each occurring in opposite directions. Overall, these results suggest that sperm mRNA transcripts are indicators of low dose toxicant-induced testicular injury in the rat. Rats were exposed to sub-chronic low doses of the Sertoli cell toxicant 2,5-hexanedione (HD) or water (control for HD) for 3 months. Some rats in each group underwent 3 months of post-exposure recovery.

			Action	DRS
	Control_RB1_1_40129.d.zip	Other
	UPA_RB1_1_40132.d.zip	Other
	checksum.txt	Txt
	peptides.pep.xml	Pepxml

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Engineering Linear Cap-independent mRNA Vaccines with Intrinsic 1 Adjuvanticity for Potent Cancer Immunotherapy

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