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Bergara-Muguruza et al. J Transl Genet Genom 2023;7:213-229 https://dx.doi.org/10.20517/jtgg.2023.14 Page 225

smaller synthetic RNA molecules that function as the lncRNA of interest, evolving as effective drugs. While
the sequence of many lncRNAs differs across species, their structures are often conserved, suggesting that
structural elements may be a primary determinant of function. Therefore, a comprehensive understanding
of how lncRNA domains interact with proteins, mRNAs, or genomic loci is essential for the rational design
of lncRNA therapies, enabling the selection of on-target sites while minimizing off-target effects .
[105]
Although numerous questions and challenges remain to be addressed, the increasing success rate of nucleic
acid therapeutics presents an exciting opportunity to explore lncRNAs as viable therapeutic targets in
various complex pathologies. Further research in this field holds promise for unlocking the therapeutic
potential of lncRNAs .
[107]

CONCLUSIONS
The understanding of the contribution of genetic variants to immune-mediated diseases has significantly
advanced in recent decades. However, the complexity of these variants and the non-coding location of most
associated SNPs have posed challenges in deciphering their functional roles in disease development . In
[13]
this line, lncRNAs, which are enriched with SNPs and participate in the regulation of immune-related
[8]
processes , have opened a new field of studying the involvement of disease-associated SNPs on lncRNA
function. Moreover, some lncRNAs have been found to be differentially expressed in patients compared to
controls [54,58,61,101] , highlighting their potential as biomarkers.

However, the specific functions of lncRNAs themselves and their regulatory mechanisms in disease
development remain largely unknown. Most experimental approaches have studied the expression patterns
of lncRNAs harboring associated SNPs in disease tissues, while functional studies assessing the effect of
associated alleles in lncRNA function and disease development have been limited . Disease-associated
[13]
SNPs can not only affect the expression of the lncRNAs, but can also influence their splicing, secondary
structure, or their ability in transcription of target genes [8,13,40,110] . Additionally, larger-scale studies across
diverse ethnic populations are required to validate the roles of genetic polymorphisms within lncRNAs [54,95] .

To sum up, identification and functional studies of disease-associated lncRNAs can help to understand the
underlying molecular mechanisms and may contribute to a broader image of the disease pathogenesis,
opening new diagnostic and therapeutic strategies.

DECLARATIONS
Authors' contributions
Substantially contributed to the conception and design of the article and interpretation of the relevant
literature: Bergara-Muguruza L, Olazagoitia-Garmendia A
Drafted the article or revised it critically for important intellectual content: Bergara-Muguruza L,
Castellanos-Rubio A, Santin I, Olazagoitia-Garmendia A

Availability of data and materials
Not applicable.

Financial support and sponsorship
This work was supported by Ministerio de Ciencia, Innovación y Universidades grant PGC2018-097573-A-
I00 (Castellanos-Rubio A), I+D+i PID2019-104475GA-I00 research grant funded by MCIN/AEI/10.13039/
501100011033 and Research Project Grant from the Basque Department of Health (2021111001) (Santin I),
UPV/EHU post-doctoral grant ESPDOC21/56 (Olazagoitia-Garmendia A) and Basque Government